https://ntp.niehs.nih.gov/go/6743

TDMS Study 05187-09 Pathology Tables


NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                                       METHYLEUGENOL                                     DATE: 07/20/98       
EXPERIMENT: 05187 TEST: 09                                                                                     TIME: 09:12:12       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-25337                              ROUTE: GAVAGE                                                  NTP C#: 60991B       
PATHOLOGIST: MISSING                                                                                           CAS: 93-15-2         
------------------------------------------------------------------------------------------------------------------------------------
                                                             CORE STUDY                                                             
               REASONS FOR REMOVAL:    25022 Accidently Killed                                                                      
                                       25018 Dosing Accident                                                                        
                                       25019 Moribund Sacrifice                                                                     
                                       25020 Natural Death                                                                          
                                       25021 Terminal Sacrifice                                                                     
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE 001    0 MG/KG                                                                       
                                       INCLUDE 002    0 MG/KG                                                                       
                                       INCLUDE 003    37 MG/KG                                                                      
                                       INCLUDE 004    37 MG/KG                                                                      
                                       INCLUDE 005    75 MG/KG                                                                      
                                       INCLUDE 006    75 MG/KG                                                                      
                                       INCLUDE 007    150     MG/KG                                                                 
                                       INCLUDE 008    150     MG/KG                                                                 
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10   
LAB: Battelle Columbus                                       METHYLEUGENOL                                     DATE: 07/20/98     
EXPERIMENT: 05187 TEST: 09                                                                                     TIME: 09:12:12     
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                      
CONT: NO1-ES-25337                              ROUTE: GAVAGE                                                  NTP C#: 60991B     
PATHOLOGIST: MISSING                                                                                           CAS: 93-15-2       
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF                  METHYLEUGENOL
===============================================================
Male Rats
------------
Organ                                 Morphology
-----                                 ----------
Adrenal Cortex                         Hyperplasia Focal
Adrenal Medulla                        Hyperplasia Focal
Blood Vessel                           Mineralization
Blood Vessel: Aorta                    Mineralization
Bone                                   Fibrous Osteodystrophy
Bone Marrow                            Hyperplasia
Heart: Myocardium                      Degeneration
                                       Mineralization
Intestine Large, Rectum                Parasite Metazoan
Intestine Small, Duodenum              Ulcer
Islets, Pancreatic                     Hyperplasia
Kidney                                 Inflammation Focal
                                       Nephropathy
Kidney: Renal Tubule                   Hyperplasia Focal
                                       Hyperplasia Oncocytic
Liver                                  Basophilic Focus
                                       Degeneration Cystic Focal
                                       Eosinophilic Focus
                                       Hepatodiaphragmatic Nodule
                                       Mixed Cell Focus
Liver: Bile Duct                       Hyperplasia
                                       Hyperplasia Atypical Focal
Liver: Centrilobular                   Degeneration
Liver: Hepatocyte                      Hypertrophy
Liver: Oval Cell                       Hyperplasia
Lung: Interstitium                     Mineralization
Mammary Gland                          Dilatation
Mesentery: Fat                         Necrosis
Nose                                   Inflammation
Pancreas: Acinus                       Atrophy
Pancreas: Artery                       Inflammation Chronic
Parathyroid Gland                      Hyperplasia
Pituitary Gland: Pars Distalis         Hyperplasia Focal
Preputial Gland                        Cyst
Prostate                               Inflammation Chronic
Salivary Glands: Submandibular Gland   Cytoplasmic Alteration
Seminal Vesicle                        Inflammation
Spleen                                 Fibrosis
                                       Hematopoietic Cell Proliferation
Stomach, Forestomach                   Mineralization
                                       Ulcer
Stomach, Glandular                     Atrophy
                                       Mineralization
Stomach, Glandular: Neuroendocrine Cell
                                       Hyperplasia
Testes: Interstitial Cell              Hyperplasia
Thyroid Gland: C-Cell                  Hyperplasia
===============================================================
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10   
LAB: Battelle Columbus                                       METHYLEUGENOL                                     DATE: 07/20/98     
EXPERIMENT: 05187 TEST: 09                                                                                     TIME: 09:12:12     
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                      
CONT: NO1-ES-25337                              ROUTE: GAVAGE                                                  NTP C#: 60991B     
PATHOLOGIST: MISSING                                                                                           CAS: 93-15-2       
Female Rats
------------
Organ                                  Morphology
-----                                  ----------
Bone Marrow                            Hyperplasia
Heart: Myocardium                      Degeneration
Kidney                                 Nephropathy
Liver                                  Basophilic Focus
                                       Clear Cell Focus
                                       Degeneration Cystic Focal
                                       Eosinophilic Focus
                                       Mixed Cell Focus
Liver: Bile Duct                       Hyperplasia
Liver: Hepatocyte                      Hypertrophy
Liver: Oval Cell                       Hyperplasia
Mammary Gland                          Hyperplasia Focal
Pituitary Gland                        Angiectasis
Pituitary Gland: Pars Distalis         Hyperplasia Focal
Salivary Glands: Submandibular Gland   Cytoplasmic Alteration
Spleen                                 Fibrosis
                                       Hematopoietic Cell Proliferation
Spleen: Red Pulp                       Necrosis
Stomach, Glandular                     Atrophy
Stomach, Glandular: Neuroendocrine Cell
                                       Hyperplasia
Thyroid Gland: C-Cell                  Hyperplasia
===============================================================
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 1
                     Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     13/50 (26%)  12/50 (24%)  6/50 (12%)   4/50 (8%)   |13/50 (26%)  11/50 (22%)  7/50 (14%)   9/49 (18%)   |
|POLY-3 ADJUSTED (b)|     30.5%        30.2%        16.0%        12.4%       |31.3%        26.7%        16.7%        24.2%        |
|TERMINAL (d)       |     9/20 (45%)   6/16 (38%)   5/15 (33%)   0/0 (0%)    |6/22 (27%)   8/25 (32%)   3/22 (14%)   3/11 (27%)   |
|FIRST INCIDENCE    |     610          639          659          642         |459          683          637          572          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.445      P=0.456      P=0.171N     P=0.275     |P=0.488      P=0.316N     P=0.111N     P=0.515      |
|POLY 3             |     P=0.019N*    P=0.584N     P=0.099N     P=0.055N    |P=0.224N     P=0.412N     P=0.091N     P=0.325N     |
|POLY 1.5           |     P=0.010N*    P=0.548N     P=0.082N     P=0.030N*   |P=0.199N     P=0.406N     P=0.095N     P=0.279N     |
|POLY 6             |     P=0.053N     P=0.565      P=0.136N     P=0.140N    |P=0.275N     P=0.427N     P=0.089N     P=0.423N     |
|LOGISTIC REGRESSION|     P=0.112N     P=0.558      P=0.142N     P=0.176N    |P=0.259N     P=0.362N     P=0.089N     P=0.306N     |
|COCH-ARM / FISHERS |     P=0.005N**   P=0.500N     P=0.062N     P=0.016N*   |P=0.183N     P=0.408N     P=0.105N     P=0.251N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    2/50 (4%)    0/50 (0%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     2.4%         2.6%         0.0%         0.0%        |0.0%         4.9%         0.0%         2.8%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    1/25 (4%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     588          650          ---          ---         |---          724          ---          660          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.286N     P=0.740      P=0.519N     P=0.539N    |P=0.415      P=0.268      (e)          P=0.457      |
|POLY 3             |     P=0.251N     P=0.744      P=0.523N     P=0.557N    |P=0.520      P=0.246      (e)          P=0.484      |
|POLY 1.5           |     P=0.245N     P=0.751      P=0.514N     P=0.530N    |P=0.530      P=0.243      (e)          P=0.492      |
|POLY 6             |     P=0.266N     P=0.734      P=0.538N     P=0.604N    |P=0.497      P=0.249      (e)          P=0.468      |
|LOGISTIC REGRESSION|     P=0.208N     P=0.740N     P=0.456N     P=0.426N    |P=0.491      P=0.255      (e)          P=0.495      |
|COCH-ARM / FISHERS |     P=0.236N     P=0.753N     P=0.500N     P=0.500N    |P=0.534      P=0.247      (e)          P=0.495      |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 2
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     16/50 (32%)  20/50 (40%)  21/50 (42%)  21/50 (42%) |4/50 (8%)    9/50 (18%)   4/50 (8%)    3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     36.1%        46.9%        50.8%        54.9%       |10.0%        20.6%        9.6%         8.3%         |
|TERMINAL (d)       |     6/20 (30%)   6/16 (38%)   9/15 (60%)   0/0 (0%)    |2/22 (9%)    3/25 (12%)   2/22 (9%)    2/11 (18%)   |
|FIRST INCIDENCE    |     553          535          521          457         |609          443          627          679          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.136      P=0.064      P<0.001 **  |P=0.439N     P=0.164      P=0.622N     P=0.551      |
|POLY 3             |     P=0.049 *    P=0.204      P=0.117      P=0.059     |P=0.265N     P=0.150      P=0.620N     P=0.556N     |
|POLY 1.5           |     P=0.102      P=0.230      P=0.145      P=0.112     |P=0.238N     P=0.137      P=0.628N     P=0.528N     |
|POLY 6             |     P=0.011 *    P=0.172      P=0.081      P=0.016 *   |P=0.319N     P=0.165      P=0.614N     P=0.609N     |
|LOGISTIC REGRESSION|     P=0.098      P=0.249      P=0.153      P=0.144     |P=0.222N     P=0.101      P=0.622N     P=0.581N     |
|COCH-ARM / FISHERS |     P=0.202      P=0.266      P=0.204      P=0.204     |P=0.223N     P=0.117      P=0.643N     P=0.511N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Blood Vessel                                                                                                                     |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    3/50 (6%)    7/50 (14%)  |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.4%         5.1%         7.8%         21.0%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     662          596          568          568         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.454      P=0.273      P<0.001 **  |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.003 **   P=0.481      P=0.278      P=0.012 *   |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.005 **   P=0.489      P=0.288      P=0.019 *   |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.002 **   P=0.469      P=0.262      P=0.005 **  |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.012 *    P=0.538      P=0.350      P=0.024 *   |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.009 **   P=0.500      P=0.309      P=0.030 *   |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 3
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Blood Vessel: Aorta                                                                                                              |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/50 (10%)   0/50 (0%)    9/50 (18%)   6/50 (12%)  |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     11.8%        0.0%         23.4%        18.5%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    2/15 (13%)   0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     626          ---          664          650         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.059N     P=0.073      P=0.003 **  |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.070      P=0.038N*    P=0.139      P=0.319     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.108      P=0.035N*    P=0.159      P=0.403     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.030 *    P=0.044N*    P=0.113      P=0.194     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.028 *    P=0.037N*    P=0.130      P=0.193     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.169      P=0.028N*    P=0.194      P=0.500     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Fibrous Osteodystrophy                                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     8/50 (16%)   2/50 (4%)    12/50 (24%)  14/50 (28%) |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     18.7%        5.1%         30.5%        39.9%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/20 (5%)    0/16 (0%)    3/15 (20%)   0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     626          596          568          568         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.100N     P=0.086      P<0.001 **  |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.002 **   P=0.060N     P=0.159      P=0.030 *   |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.005 **   P=0.053N     P=0.183      P=0.059     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P<0.001 **   P=0.072N     P=0.125      P=0.008 **  |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.002 **   P=0.050N     P=0.171      P=0.028 *   |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.013 *    P=0.046N*    P=0.227      P=0.114     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 4
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Hyperostosis                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    1/50 (2%)    5/50 (10%)   4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |2.5%         2.4%         11.5%        10.6%        |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |555          673          515          553          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.052      P=0.748N     P=0.129      P=0.153      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.062      P=0.754N     P=0.121      P=0.162      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.071      P=0.756N     P=0.113      P=0.173      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.049 *    P=0.752N     P=0.131      P=0.142      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.079      P=0.746      P=0.073      P=0.166      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.078      P=0.753N     P=0.102      P=0.181      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Osteopetrosis                                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    1/50 (2%)    2/50 (4%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.4%         5.2%         0.0%         0.0%        |0.0%         2.5%         4.8%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    1/16 (6%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    1/25 (4%)    2/22 (9%)    0/11 (0%)    |
|FIRST INCIDENCE    |     521          673          ---          ---         |---          730 (T)      730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.342N     P=0.458      P=0.513N     P=0.521N    |P=0.543      P=0.525      P=0.237      (e)          |
|POLY 3             |     P=0.227N     P=0.472      P=0.524N     P=0.558N    |P=0.640      P=0.508      P=0.249      (e)          |
|POLY 1.5           |     P=0.209N     P=0.484      P=0.514N     P=0.530N    |P=0.630N     P=0.505      P=0.245      (e)          |
|POLY 6             |     P=0.265N     P=0.455      P=0.539N     P=0.605N    |P=0.581      P=0.511      P=0.253      (e)          |
|LOGISTIC REGRESSION|     P=0.174N     P=0.523      P=0.413N     P=0.386N    |(e)          P=0.525      P=0.237      (e)          |
|COCH-ARM / FISHERS |     P=0.188N     P=0.500      P=0.500N     P=0.500N    |P=0.616N     P=0.500      P=0.247      (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 5
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Fibrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    2/49 (4%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     7.1%         0.0%         5.3%         0.0%        |5.1%         0.0%         4.9%         5.5%         |
|TERMINAL (d)       |     1/20 (5%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |1/22 (5%)    0/25 (0%)    1/22 (5%)    1/11 (9%)    |
|FIRST INCIDENCE    |     521          ---          610          ---         |641          ---          613          679          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.273N     P=0.157N     P=0.579N     P=0.521N    |P=0.280      P=0.226N     P=0.681N     P=0.508      |
|POLY 3             |     P=0.159N     P=0.134N     P=0.545N     P=0.181N    |P=0.405      P=0.230N     P=0.680N     P=0.665      |
|POLY 1.5           |     P=0.141N     P=0.127N     P=0.528N     P=0.148N    |P=0.426      P=0.232N     P=0.688N     P=0.683      |
|POLY 6             |     P=0.199N     P=0.144N     P=0.572N     P=0.250N    |P=0.372      P=0.228N     P=0.671N     P=0.629      |
|LOGISTIC REGRESSION|     P=0.115N     P=0.115N     P=0.477N     P=0.123N    |P=0.414      P=0.231N     P=0.695N     P=0.640      |
|COCH-ARM / FISHERS |     P=0.125N     P=0.121N     P=0.500N     P=0.121N    |P=0.444      P=0.247N     P=0.684      P=0.691N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     18/50 (36%)  14/50 (28%)  22/50 (44%)  23/50 (46%) |4/50 (8%)    15/50 (30%)  11/49 (22%)  20/50 (40%)  |
|POLY-3 ADJUSTED (b)|     41.4%        33.7%        53.6%        56.2%       |10.1%        34.0%        26.8%        49.6%        |
|TERMINAL (d)       |     10/20 (50%)  7/16 (44%)   10/15 (67%)  0/0 (0%)    |3/22 (14%)   8/25 (32%)   8/22 (36%)   8/11 (73%)   |
|FIRST INCIDENCE    |     564          406          522          409         |549          347          676          508          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.490N     P=0.065      P<0.001 **  |P<0.001 **   P=0.013 *    P=0.048 *    P<0.001 **   |
|POLY 3             |     P=0.035 *    P=0.304N     P=0.174      P=0.115     |P<0.001 **   P=0.007 **   P=0.046 *    P<0.001 **   |
|POLY 1.5           |     P=0.053      P=0.282N     P=0.206      P=0.156     |P<0.001 **   P=0.006 **   P=0.044 *    P<0.001 **   |
|POLY 6             |     P=0.015 *    P=0.347N     P=0.131      P=0.059     |P<0.001 **   P=0.009 **   P=0.049 *    P<0.001 **   |
|LOGISTIC REGRESSION|     P=0.045 *    P=0.302N     P=0.150      P=0.234     |P<0.001 **   P=0.005 **   P=0.058      P<0.001 **   |
|COCH-ARM / FISHERS |     P=0.081      P=0.260N     P=0.270      P=0.208     |P<0.001 **   P=0.005 **   P=0.041 *    P<0.001 **   |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 6
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Inflammation Granulomatous                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    2/50 (4%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         4.9%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    2/25 (8%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          730 (T)      ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.539N     P=0.266      (e)          (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.406N     P=0.245      (e)          (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.404N     P=0.243      (e)          (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.412N     P=0.248      (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          P=0.266      (e)          (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.406N     P=0.247      (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    2/50 (4%)    1/50 (2%)   |0/50 (0%)    1/50 (2%)    0/49 (0%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         5.1%         5.3%         3.2%        |0.0%         2.4%         0.0%         5.4%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          575          661          659         |---          637          ---          589          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.188      P=0.219      P=0.164      P=0.367     |P=0.102      P=0.505      (e)          P=0.194      |
|POLY 3             |     P=0.324      P=0.225      P=0.216      P=0.446     |P=0.132      P=0.509      (e)          P=0.223      |
|POLY 1.5           |     P=0.392      P=0.230      P=0.224      P=0.472     |P=0.137      P=0.506      (e)          P=0.232      |
|POLY 6             |     P=0.216      P=0.218      P=0.204      P=0.402     |P=0.124      P=0.514      (e)          P=0.206      |
|LOGISTIC REGRESSION|     P=0.448      P=0.257      P=0.216      P=0.472     |P=0.145      P=0.491      (e)          P=0.240      |
|COCH-ARM / FISHERS |     P=0.469      P=0.247      P=0.247      P=0.500     |P=0.140      P=0.500      (e)          P=0.247      |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 7
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow: Myeloid Cell                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    2/50 (4%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |2.5%         4.8%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |641          606          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.213N     P=0.522      P=0.495N     P=0.550N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.192N     P=0.517      P=0.494N     P=0.518N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.190N     P=0.511      P=0.497N     P=0.507N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.196N     P=0.524      P=0.490N     P=0.538N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.190N     P=0.481      P=0.514N     P=0.498N     |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.189N     P=0.500      P=0.505N     P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Hydrocephalus                                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    3/50 (6%)    1/50 (2%)   |4/50 (8%)    9/50 (18%)   3/50 (6%)    8/50 (16%)   |
|POLY-3 ADJUSTED (b)|     4.8%         7.6%         7.9%         3.1%        |10.1%        21.8%        7.1%         20.9%        |
|TERMINAL (d)       |     1/20 (5%)    1/16 (6%)    2/15 (13%)   0/0 (0%)    |1/22 (5%)    7/25 (28%)   0/22 (0%)    1/11 (9%)    |
|FIRST INCIDENCE    |     668          572          601          523         |597          637          557          541          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.452      P=0.442      P=0.390      P=0.643     |P=0.078      P=0.166      P=0.463N     P=0.066      |
|POLY 3             |     P=0.475N     P=0.476      P=0.456      P=0.592N    |P=0.255      P=0.125      P=0.466N     P=0.154      |
|POLY 1.5           |     P=0.411N     P=0.487      P=0.473      P=0.548N    |P=0.271      P=0.123      P=0.479N     P=0.169      |
|POLY 6             |     P=0.540      P=0.462      P=0.426      P=0.667N    |P=0.226      P=0.126      P=0.452N     P=0.125      |
|LOGISTIC REGRESSION|     P=0.348N     P=0.513      P=0.445      P=0.481N    |P=0.245      P=0.134      P=0.500N     P=0.167      |
|COCH-ARM / FISHERS |     P=0.343N     P=0.500      P=0.500      P=0.500N    |P=0.278      P=0.117      P=0.500N     P=0.178      |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 8
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Necrosis Focal                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    1/50 (2%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         5.1%         2.7%         3.2%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          650          658          684         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.255      P=0.220      P=0.469      P=0.202     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.375      P=0.224      P=0.481      P=0.446     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.434      P=0.229      P=0.488      P=0.472     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.279      P=0.217      P=0.469      P=0.401     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.454      P=0.240      P=0.502      P=0.384     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.500      P=0.247      P=0.500      P=0.500     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain: Hypothalamus                                                                                                              |
|     Degeneration                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    1/50 (2%)    0/50 (0%)   |9/50 (18%)   12/50 (24%)  6/50 (12%)   7/50 (14%)   |
|POLY-3 ADJUSTED (b)|     0.0%         2.6%         2.6%         0.0%        |22.4%        28.5%        14.0%        18.5%        |
|TERMINAL (d)       |     0/20 (0%)    1/16 (6%)    0/15 (0%)    0/0 (0%)    |6/22 (27%)   8/25 (32%)   1/22 (5%)    1/11 (9%)    |
|FIRST INCIDENCE    |     ---          730 (T)      601          ---         |597          609          541          541          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.624      P=0.455      P=0.476      (e)         |P=0.546      P=0.415      P=0.269N     P=0.442      |
|POLY 3             |     P=0.648      P=0.486      P=0.482      (e)         |P=0.233N     P=0.352      P=0.236N     P=0.443N     |
|POLY 1.5           |     P=0.633N     P=0.492      P=0.489      (e)         |P=0.213N     P=0.338      P=0.256N     P=0.410N     |
|POLY 6             |     P=0.530      P=0.477      P=0.470      (e)         |P=0.273N     P=0.372      P=0.215N     P=0.510N     |
|LOGISTIC REGRESSION|     P=0.630N     P=0.455      P=0.536      (e)         |P=0.240N     P=0.349      P=0.270N     P=0.476N     |
|COCH-ARM / FISHERS |     P=0.595N     P=0.500      P=0.500      (e)         |P=0.204N     P=0.312      P=0.288N     P=0.393N     |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 9
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral Gland                                                                                                                   |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |2/48 (4%)    1/46 (2%)    2/49 (4%)    1/46 (2%)    |
|POLY-3 ADJUSTED (b)|                                                        |5.2%         2.7%         4.8%         3.0%         |
|TERMINAL (d)       |                                                        |0/21 (0%)    1/22 (5%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |                                                        |597          730 (T)      557          611          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.555N     P=0.492N     P=0.679N     P=0.579N     |
|POLY 3             |                                                        |P=0.479N     P=0.515N     P=0.670N     P=0.547N     |
|POLY 1.5           |                                                        |P=0.465N     P=0.514N     P=0.676N     P=0.528N     |
|POLY 6             |                                                        |P=0.501N     P=0.518N     P=0.663N     P=0.579N     |
|LOGISTIC REGRESSION|                                                        |P=0.448N     P=0.513N     P=0.689      P=0.509N     |
|COCH-ARM / FISHERS |                                                        |P=0.454N     P=0.516N     P=0.684N     P=0.516N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral Gland                                                                                                                   |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |2/48 (4%)    3/46 (7%)    1/49 (2%)    0/46 (0%)    |
|POLY-3 ADJUSTED (b)|                                                        |5.3%         8.1%         2.5%         0.0%         |
|TERMINAL (d)       |                                                        |1/21 (5%)    3/22 (14%)   1/22 (5%)    0/11 (0%)    |
|FIRST INCIDENCE    |                                                        |717          730 (T)      730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.190N     P=0.527      P=0.485N     P=0.374N     |
|POLY 3             |                                                        |P=0.117N     P=0.486      P=0.476N     P=0.267N     |
|POLY 1.5           |                                                        |P=0.111N     P=0.485      P=0.483N     P=0.255N     |
|POLY 6             |                                                        |P=0.128N     P=0.487      P=0.469N     P=0.290N     |
|LOGISTIC REGRESSION|                                                        |P=0.167N     P=0.503      P=0.464N     P=0.340N     |
|COCH-ARM / FISHERS |                                                        |P=0.107N     P=0.480      P=0.492N     P=0.258N     |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 10
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart: Atrium                                                                                                                    |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/50 (12%)   5/50 (10%)   4/50 (8%)    2/50 (4%)   |0/50 (0%)    2/50 (4%)    1/49 (2%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     14.1%        12.7%        10.5%        6.2%        |0.0%         4.8%         2.5%         0.0%         |
|TERMINAL (d)       |     1/20 (5%)    1/16 (6%)    1/15 (7%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     553          575          596          502         |---          520          712          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.542      P=0.614      P=0.561N     P=0.660N    |P=0.546N     P=0.258      P=0.523      (e)          |
|POLY 3             |     P=0.175N     P=0.556N     P=0.443N     P=0.241N    |P=0.483N     P=0.249      P=0.508      (e)          |
|POLY 1.5           |     P=0.131N     P=0.531N     P=0.414N     P=0.184N    |P=0.471N     P=0.245      P=0.503      (e)          |
|POLY 6             |     P=0.273N     P=0.589N     P=0.492N     P=0.366N    |P=0.507N     P=0.254      P=0.513      (e)          |
|LOGISTIC REGRESSION|     P=0.113N     P=0.508N     P=0.393N     P=0.110N    |P=0.465N     P=0.220      P=0.513      (e)          |
|COCH-ARM / FISHERS |     P=0.092N     P=0.500N     P=0.370N     P=0.134N    |P=0.467N     P=0.247      P=0.495      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart: Myocardium                                                                                                                |
|     Degeneration                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     45/50 (90%)  41/50 (82%)  34/50 (68%)  37/50 (74%) |35/50 (70%)  30/50 (60%)  26/49 (53%)  20/49 (41%)  |
|POLY-3 ADJUSTED (b)|     92.7%        85.4%        72.4%        81.0%       |77.5%        68.9%        59.3%        49.8%        |
|TERMINAL (d)       |     19/20 (95%)  14/16 (88%)  9/15 (60%)   0/0 (0%)    |16/22 (73%)  20/25 (80%)  15/22 (68%)  7/11 (64%)   |
|FIRST INCIDENCE    |     521          403          438          409         |459          450          515          508          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.367      P=0.469N     P<0.001 **  |P=0.333N     P=0.121N     P=0.074N     P=0.331N     |
|POLY 3             |     P=0.047N*    P=0.187N     P=0.005N**   P=0.059N    |P=0.002N**   P=0.234N     P=0.043N*    P=0.003N**   |
|POLY 1.5           |     P=0.033N*    P=0.175N     P=0.006N**   P=0.040N*   |P<0.001N**   P=0.201N     P=0.045N*    P=0.002N**   |
|POLY 6             |     P=0.093N     P=0.228N     P=0.007N**   P=0.131N    |P=0.006N**   P=0.316N     P=0.049N*    P=0.012N*    |
|LOGISTIC REGRESSION|     P=0.029N*    P=0.219N     P=0.009N**   P=0.062N    |P=0.003N**   P=0.127N     P=0.035N*    P=0.004N**   |
|COCH-ARM / FISHERS |     P=0.026N*    P=0.194N     P=0.006N**   P=0.033N*   |P=0.002N**   P=0.201N     P=0.063N     P=0.003N**   |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 11
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart: Myocardium                                                                                                                |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/50 (10%)   2/50 (4%)    11/50 (22%)  9/50 (18%)  |0/50 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     11.8%        5.1%         27.8%        26.8%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    2/15 (13%)   0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     626          596          568          598         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.316N     P=0.031 *    P<0.001 **  |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.013 *    P=0.247N     P=0.059      P=0.084     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.024 *    P=0.233N     P=0.067      P=0.128     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.004 **   P=0.268N     P=0.048 *    P=0.037 *   |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.018 *    P=0.223N     P=0.068      P=0.069     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.050      P=0.218N     P=0.086      P=0.194     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large, Colon                                                                                                           |
|     Parasite Metazoan                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    5/50 (10%)   1/50 (2%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     2.4%         5.1%         12.6%        3.1%        |2.5%         0.0%         0.0%         2.8%         |
|TERMINAL (d)       |     1/20 (5%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    1/11 (9%)    |
|FIRST INCIDENCE    |     730 (T)      638          502          568         |719          ---          ---          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.322      P=0.445      P=0.081      P=0.481     |P=0.476      P=0.484N     P=0.500N     P=0.618      |
|POLY 3             |     P=0.372      P=0.480      P=0.090      P=0.698     |P=0.579      P=0.492N     P=0.490N     P=0.743      |
|POLY 1.5           |     P=0.468      P=0.488      P=0.094      P=0.730     |P=0.587      P=0.495N     P=0.493N     P=0.754      |
|POLY 6             |     P=0.221      P=0.469      P=0.083      P=0.637     |P=0.568      P=0.490N     P=0.486N     P=0.721      |
|LOGISTIC REGRESSION|     P=0.534N     P=0.485      P=0.135      P=0.774     |P=0.515      P=0.487N     P=0.484N     P=0.664      |
|COCH-ARM / FISHERS |     P=0.569      P=0.500      P=0.102      P=0.753N    |P=0.595      P=0.500N     P=0.500N     P=0.753N     |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 12
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large, Rectum                                                                                                          |
|     Parasite Metazoan                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/49 (2%)    3/49 (6%)    5/49 (10%)   4/50 (8%)   |2/50 (4%)    4/50 (8%)    2/50 (4%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     2.5%         7.7%         13.0%        12.1%       |5.0%         9.8%         4.7%         5.4%         |
|TERMINAL (d)       |     1/20 (5%)    1/16 (6%)    2/15 (13%)   0/0 (0%)    |1/22 (5%)    4/25 (16%)   0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     730 (T)      403          521          502         |619          730 (T)      541          548          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.010 *    P=0.246      P=0.071      P=0.030 *   |P=0.549      P=0.388      P=0.665N     P=0.605      |
|POLY 3             |     P=0.079      P=0.291      P=0.087      P=0.121     |P=0.480N     P=0.350      P=0.672N     P=0.672      |
|POLY 1.5           |     P=0.113      P=0.298      P=0.092      P=0.150     |P=0.465N     P=0.347      P=0.680N     P=0.686      |
|POLY 6             |     P=0.039 *    P=0.280      P=0.079      P=0.081     |P=0.508N     P=0.352      P=0.664N     P=0.643      |
|LOGISTIC REGRESSION|     P=0.210      P=0.323      P=0.110      P=0.223     |P=0.458N     P=0.362      P=0.680      P=0.692N     |
|COCH-ARM / FISHERS |     P=0.162      P=0.309      P=0.102      P=0.187     |P=0.456N     P=0.339      P=0.691N     P=0.691N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small, Duodenum                                                                                                        |
|     Ulcer                                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     7.2%         2.6%         0.0%         0.0%        |0.0%         2.4%         0.0%         0.0%         |
|TERMINAL (d)       |     1/20 (5%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     722          680          ---          ---         |---          520          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.159N     P=0.397N     P=0.193N     P=1.000     |P=0.562N     P=0.509      (e)          (e)          |
|POLY 3             |     P=0.046N*    P=0.329N     P=0.138N     P=0.177N    |P=0.559N     P=0.511      (e)          (e)          |
|POLY 1.5           |     P=0.045N*    P=0.319N     P=0.130N     P=0.146N    |P=0.562N     P=0.507      (e)          (e)          |
|POLY 6             |     P=0.048N*    P=0.344N     P=0.151N     P=0.244N    |P=0.553N     P=0.515      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.103N     P=0.365N     P=0.199N     P=0.961N    |P=0.621N     P=0.437      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.044N*    P=0.309N     P=0.121N     P=0.121N    |P=0.567N     P=0.500      (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 13
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    4/50 (8%)    1/50 (2%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         10.2%        2.6%         0.0%        |2.5%         0.0%         0.0%         2.8%         |
|TERMINAL (d)       |     0/20 (0%)    2/16 (13%)   0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    1/11 (9%)    |
|FIRST INCIDENCE    |     ---          589          568          ---         |616          ---          ---          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.580N     P=0.047 *    P=0.496      (e)         |P=0.515      P=0.495N     P=0.485N     P=0.664      |
|POLY 3             |     P=0.416N     P=0.053      P=0.482      (e)         |P=0.579      P=0.494N     P=0.492N     P=0.741      |
|POLY 1.5           |     P=0.356N     P=0.056      P=0.489      (e)         |P=0.587      P=0.496N     P=0.494N     P=0.753      |
|POLY 6             |     P=0.534N     P=0.049 *    P=0.471      (e)         |P=0.567      P=0.493N     P=0.489N     P=0.717      |
|LOGISTIC REGRESSION|     P=0.304N     P=0.058      P=0.556      (e)         |P=0.591      P=0.517N     P=0.518N     P=0.754      |
|COCH-ARM / FISHERS |     P=0.296N     P=0.059      P=0.500      (e)         |P=0.595      P=0.500N     P=0.500N     P=0.753N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Hydronephrosis                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    2/50 (4%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         5.3%         0.0%        |0.0%         4.8%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    1/25 (4%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          ---          664          ---         |---          450          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.293      (e)          P=0.165      (e)         |P=0.460N     P=0.256      (e)          (e)          |
|POLY 3             |     P=0.443      (e)          P=0.216      (e)         |P=0.406N     P=0.250      (e)          (e)          |
|POLY 1.5           |     P=0.520      (e)          P=0.224      (e)         |P=0.404N     P=0.246      (e)          (e)          |
|POLY 6             |     P=0.307      (e)          P=0.204      (e)         |P=0.411N     P=0.254      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.516      (e)          P=0.216      (e)         |P=0.429N     P=0.204      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.595      (e)          P=0.247      (e)         |P=0.409N     P=0.247      (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 14
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Infarct                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    3/50 (6%)    1/50 (2%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         7.2%         2.4%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    1/22 (5%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          520          730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.449N     P=0.136      P=0.500      (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.386N     P=0.130      P=0.510      (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.374N     P=0.126      P=0.507      (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.412N     P=0.136      P=0.514      (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.370N     P=0.106      P=0.500      (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.372N     P=0.121      P=0.500      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Inflammation Focal                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    1/50 (2%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.6%         2.7%         6.3%        |0.0%         0.0%         2.4%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          650          712          575         |---          ---          690          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.032 *    P=0.483      P=0.388      P=0.129     |P=0.662      (e)          P=0.520      (e)          |
|POLY 3             |     P=0.104      P=0.487      P=0.480      P=0.184     |P=0.652      (e)          P=0.511      (e)          |
|POLY 1.5           |     P=0.126      P=0.493      P=0.488      P=0.208     |P=0.676      (e)          P=0.507      (e)          |
|POLY 6             |     P=0.074      P=0.480      P=0.467      P=0.148     |P=0.603      (e)          P=0.516      (e)          |
|LOGISTIC REGRESSION|     P=0.142      P=0.509      P=0.449      P=0.268     |P=0.687      (e)          P=0.508      (e)          |
|COCH-ARM / FISHERS |     P=0.153      P=0.500      P=0.500      P=0.247     |P=0.692      (e)          P=0.500      (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 15
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Nephropathy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     49/50 (98%)  46/50 (92%)  48/50 (96%)  50/50 (100%)|35/50 (70%)  42/50 (84%)  41/50 (82%)  44/49 (90%)  |
|POLY-3 ADJUSTED (b)|     99.8%        95.8%        98.5%        100.0%      |80.5%        90.4%        87.7%        94.3%        |
|TERMINAL (d)       |     20/20 (100%) 16/16 (100%) 15/15 (100%) 0/0 (0%)    |22/22 (100%) 25/25 (100%) 22/22 (100%) 11/11 (100%) |
|FIRST INCIDENCE    |     521          403          438          337         |459          347          444          508          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.268      P=0.095      P<0.001 **  |P<0.001 **   P=0.349      P=0.244      P<0.001 **   |
|POLY 3             |     P=0.387      P=0.192N     P=0.707N     P=1.000     |P=0.029 *    P=0.112      P=0.229      P=0.022 *    |
|POLY 1.5           |     P=0.277      P=0.155N     P=0.699N     P=0.981     |P=0.023 *    P=0.099      P=0.174      P=0.017 *    |
|POLY 6             |     P=0.558      P=0.374N     P=0.841N     P=1.000     |P=0.044 *    P=0.133      P=0.330      P=0.033 *    |
|LOGISTIC REGRESSION|     P=0.066      P=0.255N     P=0.773N     P=0.431     |P=0.009 **   P=0.102      P=0.192      P=0.006 **   |
|COCH-ARM / FISHERS |     P=0.199      P=0.181N     P=0.500N     P=0.500     |P=0.016 *    P=0.077      P=0.121      P=0.013 *    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         5.2%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    1/16 (6%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          725          ---          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.752      P=0.193      (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.464N     P=0.221      (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.437N     P=0.228      (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.516N     P=0.211      (e)          (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.746      P=0.180      (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.405N     P=0.247      (e)          (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 16
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/50 (10%)   1/50 (2%)    7/50 (14%)   4/50 (8%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     11.9%        2.6%         18.6%        12.4%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     2/20 (10%)   1/16 (6%)    5/15 (33%)   0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     642          730 (T)      673          646         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.003 **   P=0.158N     P=0.195      P=0.064     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.312      P=0.121N     P=0.301      P=0.611     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.392      P=0.112N     P=0.332      P=0.587N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.193      P=0.136N     P=0.251      P=0.471     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.103      P=0.125N     P=0.235      P=0.508     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.483      P=0.102N     P=0.380      P=0.500N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Hyperplasia Oncocytic                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         6.3%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          642         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.019 *    (e)          (e)          P=0.132     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.037 *    (e)          (e)          P=0.183     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.041 *    (e)          (e)          P=0.208     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.034 *    (e)          (e)          P=0.147     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.041 *    (e)          (e)          P=0.209     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.046 *    (e)          (e)          P=0.247     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 17
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Pigmentation Lipofuscin                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    1/50 (2%)    4/50 (8%)    3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |2.5%         2.4%         9.3%         8.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |569          569          515          534          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.143      P=0.751N     P=0.212      P=0.304      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.139      P=0.752N     P=0.202      P=0.285      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.151      P=0.755N     P=0.193      P=0.295      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.116      P=0.750N     P=0.213      P=0.262      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.123      P=0.728      P=0.137      P=0.209      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.157      P=0.753N     P=0.181      P=0.301      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Basophilic Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     23/50 (46%)  21/50 (42%)  22/50 (44%)  7/50 (14%)  |36/50 (72%)  36/50 (72%)  29/49 (59%)  17/49 (35%)  |
|POLY-3 ADJUSTED (b)|     52.4%        47.5%        52.6%        20.3%       |80.9%        78.1%        66.5%        41.8%        |
|TERMINAL (d)       |     14/20 (70%)  9/16 (56%)   11/15 (73%)  0/0 (0%)    |21/22 (96%)  23/25 (92%)  20/22 (91%)  5/11 (46%)   |
|FIRST INCIDENCE    |     564          403          467          337         |241          347          444          483          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.359      P=0.443      P=0.247      P=0.277     |P=0.079N     P=0.321N     P=0.097N     P=0.120N     |
|POLY 3             |     P=0.005N**   P=0.398N     P=0.583      P=0.002N**  |P<0.001N**   P=0.465N     P=0.076N     P<0.001N**   |
|POLY 1.5           |     P<0.001N**   P=0.402N     P=0.560N     P<0.001N**  |P<0.001N**   P=0.519N     P=0.100N     P<0.001N**   |
|POLY 6             |     P=0.036N*    P=0.408N     P=0.520      P=0.013N*   |P<0.001N**   P=0.393N     P=0.052N     P<0.001N**   |
|LOGISTIC REGRESSION|     P<0.001N**   P=0.438N     P=0.526      P=0.003N**  |P<0.001N**   P=0.523N     P=0.071N     P<0.001N**   |
|COCH-ARM / FISHERS |     P<0.001N**   P=0.420N     P=0.500N     P<0.001N**  |P<0.001N**   P=0.588N     P=0.129N     P<0.001N**   |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 18
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Clear Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    3/50 (6%)    7/50 (14%)   3/50 (6%)   |3/50 (6%)    10/50 (20%)  12/49 (24%)  4/49 (8%)    |
|POLY-3 ADJUSTED (b)|     9.5%         7.5%         18.0%        9.2%        |7.5%         23.6%        29.3%        10.5%        |
|TERMINAL (d)       |     1/20 (5%)    0/16 (0%)    2/15 (13%)   0/0 (0%)    |1/22 (5%)    7/25 (28%)   9/22 (41%)   0/11 (0%)    |
|FIRST INCIDENCE    |     610          579          595          583         |549          347          690          508          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.166      P=0.589N     P=0.140      P=0.246     |P=0.229      P=0.060      P=0.015 *    P=0.426      |
|POLY 3             |     P=0.422      P=0.526N     P=0.214      P=0.635N    |P=0.526      P=0.041 *    P=0.010 *    P=0.472      |
|POLY 1.5           |     P=0.516      P=0.515N     P=0.231      P=0.571N    |P=0.547N     P=0.039 *    P=0.010 *    P=0.486      |
|POLY 6             |     P=0.269      P=0.542N     P=0.189      P=0.559     |P=0.442      P=0.042 *    P=0.010 *    P=0.438      |
|LOGISTIC REGRESSION|     P=0.509N     P=0.469N     P=0.225      P=0.515N    |P=0.551N     P=0.037 *    P=0.015 *    P=0.454      |
|COCH-ARM / FISHERS |     P=0.517N     P=0.500N     P=0.262      P=0.500N    |P=0.533N     P=0.036 *    P=0.010 *    P=0.489      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Degeneration Cystic Focal                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    2/50 (4%)    25/50 (50%)  38/50 (76%) |0/50 (0%)    0/50 (0%)    1/49 (2%)    4/49 (8%)    |
|POLY-3 ADJUSTED (b)|     9.5%         5.1%         59.1%        84.5%       |0.0%         0.0%         2.5%         10.8%        |
|TERMINAL (d)       |     0/20 (0%)    1/16 (6%)    8/15 (53%)   0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     626          650          502          409         |---          ---          717          611          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.421N     P<0.001 **   P<0.001 **  |P=0.002 **   (e)          P=0.508      P=0.039 *    |
|POLY 3             |     P<0.001 **   P=0.375N     P<0.001 **   P<0.001 **  |P=0.004 **   (e)          P=0.508      P=0.052      |
|POLY 1.5           |     P<0.001 **   P=0.358N     P<0.001 **   P<0.001 **  |P=0.005 **   (e)          P=0.503      P=0.056      |
|POLY 6             |     P<0.001 **   P=0.400N     P<0.001 **   P<0.001 **  |P=0.004 **   (e)          P=0.513      P=0.045 *    |
|LOGISTIC REGRESSION|     P<0.001 **   P=0.357N     P<0.001 **   P<0.001 **  |P=0.005 **   (e)          P=0.514      P=0.060      |
|COCH-ARM / FISHERS |     P<0.001 **   P=0.339N     P<0.001 **   P<0.001 **  |P=0.005 **   (e)          P=0.495      P=0.056      |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 19
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Eosinophilic Focus                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     11/50 (22%)  28/50 (56%)  43/50 (86%)  47/50 (94%) |10/50 (20%)  20/50 (40%)  27/49 (55%)  31/49 (63%)  |
|POLY-3 ADJUSTED (b)|     26.4%        62.9%        92.8%        96.6%       |25.1%        47.9%        62.8%        71.2%        |
|TERMINAL (d)       |     7/20 (35%)   11/16 (69%)  15/15 (100%) 0/0 (0%)    |6/22 (27%)   16/25 (64%)  18/22 (82%)  6/11 (55%)   |
|FIRST INCIDENCE    |     704          406          467          337         |679          618          444          508          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P=0.049 *    P<0.001 **   P<0.001 **   |
|POLY 3             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P=0.023 *    P<0.001 **   P<0.001 **   |
|POLY 1.5           |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P=0.024 *    P<0.001 **   P<0.001 **   |
|POLY 6             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P=0.022 *    P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION|     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P=0.027 *    P<0.001 **   P<0.001 **   |
|COCH-ARM / FISHERS |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P=0.024 *    P<0.001 **   P<0.001 **   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatodiaphragmatic Nodule                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    1/50 (2%)    0/50 (0%)    0/50 (0%)   |7/50 (14%)   2/50 (4%)    6/49 (12%)   2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     9.4%         2.6%         0.0%         0.0%        |17.0%        4.8%         14.2%        5.4%         |
|TERMINAL (d)       |     0/20 (0%)    1/16 (6%)    0/15 (0%)    0/0 (0%)    |2/22 (9%)    1/25 (4%)    2/22 (9%)    0/11 (0%)    |
|FIRST INCIDENCE    |     614          730 (T)      ---          ---         |459          450          541          508          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.043N*    P=0.229N     P=0.085N     P=0.142N    |P=0.226N     P=0.076N     P=0.474N     P=0.164N     |
|POLY 3             |     P=0.020N*    P=0.211N     P=0.079N     P=0.111N    |P=0.157N     P=0.074N     P=0.479N     P=0.104N     |
|POLY 1.5           |     P=0.019N*    P=0.196N     P=0.071N     P=0.083N    |P=0.141N     P=0.075N     P=0.492N     P=0.091N     |
|POLY 6             |     P=0.023N*    P=0.235N     P=0.095N     P=0.179N    |P=0.189N     P=0.076N     P=0.466N     P=0.134N     |
|LOGISTIC REGRESSION|     P=0.017N*    P=0.166N     P=0.049N*    P=0.041N*   |P=0.131N     P=0.092N     P=0.546N     P=0.085N     |
|COCH-ARM / FISHERS |     P=0.019N*    P=0.181N     P=0.059N     P=0.059N    |P=0.131N     P=0.080N     P=0.516N     P=0.085N     |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 20
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Mixed Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    7/50 (14%)   14/50 (28%)  8/50 (16%)  |6/50 (12%)   4/50 (8%)    19/49 (39%)  9/49 (18%)   |
|POLY-3 ADJUSTED (b)|     2.4%         17.2%        34.1%        22.2%       |15.1%        9.6%         44.0%        23.3%        |
|TERMINAL (d)       |     1/20 (5%)    3/16 (19%)   5/15 (33%)   0/0 (0%)    |2/22 (9%)    2/25 (8%)    12/22 (55%)  3/11 (27%)   |
|FIRST INCIDENCE    |     730 (T)      535          438          337         |683          564          444          527          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.022 *    P<0.001 **   P=0.003 **  |P=0.007 **   P=0.316N     P=0.005 **   P=0.096      |
|POLY 3             |     P=0.008 **   P=0.027 *    P<0.001 **   P=0.007 **  |P=0.062      P=0.337N     P=0.003 **   P=0.263      |
|POLY 1.5           |     P=0.017 *    P=0.028 *    P<0.001 **   P=0.011 *   |P=0.075      P=0.348N     P=0.002 **   P=0.276      |
|POLY 6             |     P=0.002 **   P=0.025 *    P<0.001 **   P=0.003 **  |P=0.040 *    P=0.324N     P=0.004 **   P=0.229      |
|LOGISTIC REGRESSION|     P=0.082      P=0.036 *    P<0.001 **   P=0.081     |P=0.076      P=0.345N     P=0.003 **   P=0.256      |
|COCH-ARM / FISHERS |     P=0.035 *    P=0.030 *    P<0.001 **   P=0.015 *   |P=0.090      P=0.370N     P=0.002 **   P=0.274      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Necrosis Focal                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    5/50 (10%)   3/50 (6%)   |0/50 (0%)    1/50 (2%)    1/49 (2%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     4.8%         5.1%         12.9%        9.2%        |0.0%         2.5%         2.5%         0.0%         |
|TERMINAL (d)       |     2/20 (10%)   0/16 (0%)    1/15 (7%)    0/0 (0%)    |0/22 (0%)    1/25 (4%)    1/22 (5%)    0/11 (0%)    |
|FIRST INCIDENCE    |     730 (T)      650          595          546         |---          730 (T)      730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.052      P=0.636      P=0.138      P=0.063     |P=0.678      P=0.525      P=0.500      (e)          |
|POLY 3             |     P=0.211      P=0.674      P=0.188      P=0.392     |P=0.615N     P=0.508      P=0.507      (e)          |
|POLY 1.5           |     P=0.271      P=0.682      P=0.198      P=0.444     |P=0.604N     P=0.505      P=0.503      (e)          |
|POLY 6             |     P=0.126      P=0.663      P=0.172      P=0.306     |P=0.634N     P=0.511      P=0.512      (e)          |
|LOGISTIC REGRESSION|     P=0.344      P=0.668      P=0.202      P=0.508     |(e)          P=0.525      P=0.500      (e)          |
|COCH-ARM / FISHERS |     P=0.344      P=0.691N     P=0.218      P=0.500     |P=0.600N     P=0.500      P=0.495      (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 21
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Bile Duct                                                                                                                 |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     36/50 (72%)  17/50 (34%)  16/50 (32%)  17/50 (34%) |11/50 (22%)  11/50 (22%)  17/49 (35%)  22/49 (45%)  |
|POLY-3 ADJUSTED (b)|     77.0%        40.8%        39.3%        46.4%       |27.0%        26.2%        39.4%        54.3%        |
|TERMINAL (d)       |     16/20 (80%)  6/16 (38%)   6/15 (40%)   0/0 (0%)    |6/22 (27%)   7/25 (28%)   8/22 (36%)   9/11 (82%)   |
|FIRST INCIDENCE    |     521          575          572          583         |569          609          444          508          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.135      P=0.020N*    P=0.024N*    P=0.014 *   |P<0.001 **   P=0.491N     P=0.180      P<0.001 **   |
|POLY 3             |     P=0.002N**   P<0.001N**   P<0.001N**   P<0.001N**  |P=0.002 **   P=0.568N     P=0.160      P=0.008 **   |
|POLY 1.5           |     P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**  |P=0.002 **   P=0.575N     P=0.143      P=0.010 *    |
|POLY 6             |     P=0.008N**   P<0.001N**   P<0.001N**   P=0.013N*   |P<0.001 **   P=0.565N     P=0.180      P=0.004 **   |
|LOGISTIC REGRESSION|     P=0.008N**   P<0.001N**   P<0.001N**   P=0.004N**  |P=0.002 **   P=0.557N     P=0.143      P=0.008 **   |
|COCH-ARM / FISHERS |     P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**  |P=0.003 **   P=0.595N     P=0.119      P=0.013 *    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Bile Duct                                                                                                                 |
|     Hyperplasia Atypical Focal                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         2.6%         6.2%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          ---          438          502         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.047 *    (e)          P=0.500      P=0.155     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.048 *    (e)          P=0.483      P=0.185     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.058      (e)          P=0.490      P=0.209     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.036 *    (e)          P=0.472      P=0.149     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.099      (e)          P=0.645      P=0.321     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.070      (e)          P=0.500      P=0.247     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 22
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Centrilobular                                                                                                             |
|     Degeneration                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/50 (12%)   1/50 (2%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     14.1%        2.6%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/20 (5%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     553          703          ---          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.022N*    P=0.105N     P=0.043N*    P=0.268N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.003N**   P=0.071N     P=0.023N*    P=0.039N*   |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.003N**   P=0.064N     P=0.019N*    P=0.025N*   |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.004N**   P=0.083N     P=0.029N*    P=0.083N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.005N**   P=0.063N     P=0.019N*    P=0.027N*   |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.004N**   P=0.056N     P=0.013N*    P=0.013N*   |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Centrilobular                                                                                                             |
|     Degeneration Fatty                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |0/50 (0%)    3/50 (6%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     4.8%         0.0%         2.6%         0.0%        |0.0%         7.2%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     626          ---          596          ---         |---          606          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.233N     P=0.264N     P=0.533N     P=0.321N    |P=0.343N     P=0.140      (e)          (e)          |
|POLY 3             |     P=0.208N     P=0.257N     P=0.538N     P=0.309N    |P=0.313N     P=0.130      (e)          (e)          |
|POLY 1.5           |     P=0.198N     P=0.248N     P=0.523N     P=0.273N    |P=0.311N     P=0.126      (e)          (e)          |
|POLY 6             |     P=0.232N     P=0.271N     P=0.563N     P=0.380N    |P=0.322N     P=0.137      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.160N     P=0.217N     P=0.457N     P=0.199N    |P=0.322N     P=0.106      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.188N     P=0.247N     P=0.500N     P=0.247N    |P=0.317N     P=0.121      (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 23
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Centrilobular                                                                                                             |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    4/50 (8%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    1/49 (2%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     2.4%         10.1%        0.0%         3.2%        |0.0%         0.0%         2.5%         2.8%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    1/11 (9%)    |
|FIRST INCIDENCE    |     715          575          ---          575         |---          ---          712          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.621      P=0.136      P=0.610N     P=0.477     |P=0.126      (e)          P=0.523      P=0.362      |
|POLY 3             |     P=0.418N     P=0.165      P=0.521N     P=0.698     |P=0.208      (e)          P=0.508      P=0.482      |
|POLY 1.5           |     P=0.379N     P=0.171      P=0.513N     P=0.729     |P=0.222      (e)          P=0.503      P=0.491      |
|POLY 6             |     P=0.482N     P=0.158      P=0.535N     P=0.636     |P=0.183      (e)          P=0.513      P=0.465      |
|LOGISTIC REGRESSION|     P=0.318N     P=0.188      P=0.556N     P=0.777N    |P=0.161      (e)          P=0.513      P=0.362      |
|COCH-ARM / FISHERS |     P=0.337N     P=0.181      P=0.500N     P=0.753N    |P=0.232      (e)          P=0.495      P=0.495      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Hepatocyte                                                                                                                |
|     Hypertrophy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    13/50 (26%)  25/50 (50%)  30/50 (60%) |1/50 (2%)    13/50 (26%)  16/49 (33%)  26/49 (53%)  |
|POLY-3 ADJUSTED (b)|     0.0%         30.1%        58.8%        70.4%       |2.5%         30.6%        37.9%        61.1%        |
|TERMINAL (d)       |     0/20 (0%)    4/16 (25%)   14/15 (93%)  0/0 (0%)    |1/22 (5%)    10/25 (40%)  12/22 (55%)  7/11 (64%)   |
|FIRST INCIDENCE    |     ---          403          438          337         |730 (T)      347          444          483          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 3             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 1.5           |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 6             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION|     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCH-ARM / FISHERS |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 24
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Oval Cell                                                                                                                 |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     14/50 (28%)  17/50 (34%)  24/50 (48%)  34/50 (68%) |1/50 (2%)    15/50 (30%)  19/49 (39%)  35/49 (71%)  |
|POLY-3 ADJUSTED (b)|     31.5%        38.1%        52.9%        76.1%       |2.5%         36.0%        44.3%        77.7%        |
|TERMINAL (d)       |     5/20 (25%)   2/16 (13%)   6/15 (40%)   0/0 (0%)    |1/22 (5%)    14/25 (56%)  12/22 (55%)  10/11 (91%)  |
|FIRST INCIDENCE    |     521          431          438          337         |730 (T)      347          444          483          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.217      P=0.017 *    P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 3             |     P<0.001 **   P=0.333      P=0.028 *    P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 1.5           |     P<0.001 **   P=0.332      P=0.027 *    P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 6             |     P<0.001 **   P=0.340      P=0.029 *    P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION|     P<0.001 **   P=0.427      P=0.051      P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCH-ARM / FISHERS |     P<0.001 **   P=0.333      P=0.032 *    P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    3/50 (6%)    2/50 (4%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     2.4%         7.6%         5.2%         3.2%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     639          542          568          699         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.444      P=0.264      P=0.467      P=0.512     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.574      P=0.284      P=0.468      P=0.693     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.541N     P=0.294      P=0.480      P=0.727     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.443      P=0.272      P=0.448      P=0.627     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.451N     P=0.329      P=0.542      P=0.727     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.474N     P=0.309      P=0.500      P=0.753N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 25
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Inflammation Acute                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    2/49 (4%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |2.5%         0.0%         4.9%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |700          ---          690          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.552N     P=0.493N     P=0.531      P=0.577N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.496N     P=0.493N     P=0.515      P=0.518N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.479N     P=0.495N     P=0.506      P=0.509N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.526N     P=0.491N     P=0.525      P=0.537N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.490N     P=0.491N     P=0.510      P=0.539N     |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.467N     P=0.500N     P=0.492      P=0.505N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Inflammation Granulomatous                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    2/50 (4%)    3/50 (6%)   |1/50 (2%)    0/50 (0%)    1/49 (2%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     4.8%         0.0%         5.3%         9.3%        |2.5%         0.0%         2.5%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     668          ---          610          502         |641          ---          724          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.052      P=0.288N     P=0.610      P=0.071     |P=0.484N     P=0.500N     P=0.757N     P=0.550N     |
|POLY 3             |     P=0.179      P=0.254N     P=0.662      P=0.386     |P=0.424N     P=0.494N     P=0.754N     P=0.519N     |
|POLY 1.5           |     P=0.205      P=0.247N     P=0.674      P=0.440     |P=0.417N     P=0.496N     P=0.758N     P=0.510N     |
|POLY 6             |     P=0.142      P=0.266N     P=0.641      P=0.295     |P=0.435N     P=0.492N     P=0.751N     P=0.538N     |
|LOGISTIC REGRESSION|     P=0.248      P=0.255N     P=0.696N     P=0.494     |P=0.417N     P=0.508N     P=0.761N     P=0.503N     |
|COCH-ARM / FISHERS |     P=0.237      P=0.247N     P=0.691N     P=0.500     |P=0.410N     P=0.500N     P=0.747      P=0.505N     |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 26
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung: Alveolar Epithelium                                                                                                        |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    1/50 (2%)    2/50 (4%)   |2/50 (4%)    3/50 (6%)    7/49 (14%)   3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.6%         2.6%         6.2%        |5.1%         7.3%         17.2%        8.0%         |
|TERMINAL (d)       |     0/20 (0%)    1/16 (6%)    0/15 (0%)    0/0 (0%)    |1/22 (5%)    2/25 (8%)    6/22 (27%)   0/11 (0%)    |
|FIRST INCIDENCE    |     ---          730 (T)      522          575         |644          588          717          527          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.059      P=0.455      P=0.487      P=0.190     |P=0.142      P=0.547      P=0.083      P=0.393      |
|POLY 3             |     P=0.105      P=0.486      P=0.483      P=0.185     |P=0.319      P=0.520      P=0.083      P=0.473      |
|POLY 1.5           |     P=0.126      P=0.492      P=0.489      P=0.209     |P=0.347      P=0.513      P=0.080      P=0.487      |
|POLY 6             |     P=0.075      P=0.477      P=0.471      P=0.149     |P=0.263      P=0.527      P=0.086      P=0.441      |
|LOGISTIC REGRESSION|     P=0.181      P=0.455      P=0.586      P=0.289     |P=0.329      P=0.512      P=0.095      P=0.489      |
|COCH-ARM / FISHERS |     P=0.153      P=0.500      P=0.500      P=0.247     |P=0.362      P=0.500      P=0.075      P=0.490      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung: Interstitium                                                                                                               |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    2/50 (4%)    1/50 (2%)   |0/50 (0%)    1/50 (2%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     4.8%         2.6%         5.3%         3.2%        |0.0%         2.5%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    1/15 (7%)    0/0 (0%)    |0/22 (0%)    1/25 (4%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     652          703          712          584         |---          730 (T)      ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.312      P=0.575N     P=0.544      P=0.696     |P=0.678N     P=0.525      (e)          (e)          |
|POLY 3             |     P=0.527N     P=0.527N     P=0.654      P=0.594N    |P=0.563N     P=0.508      (e)          (e)          |
|POLY 1.5           |     P=0.488N     P=0.515N     P=0.670      P=0.549N    |P=0.566N     P=0.505      (e)          (e)          |
|POLY 6             |     P=0.566      P=0.545N     P=0.626      P=0.671N    |P=0.558N     P=0.511      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.569N     P=0.519N     P=0.638      P=0.502N    |(e)          P=0.525      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.444N     P=0.500N     P=0.691N     P=0.500N    |P=0.571N     P=0.500      (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 27
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung: Interstitium                                                                                                               |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    1/50 (2%)    8/50 (16%)   10/50 (20%) |0/50 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     9.5%         2.6%         20.7%        29.8%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    2/15 (13%)   0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     626          596          595          646         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.245N     P=0.081      P<0.001 **  |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.002 **   P=0.202N     P=0.134      P=0.022 *   |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.004 **   P=0.192N     P=0.150      P=0.040 *   |(e)          (e)          (e)          (e)          |
|POLY 6             |     P<0.001 **   P=0.219N     P=0.111      P=0.007 **  |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.002 **   P=0.172N     P=0.143      P=0.011 *   |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.009 **   P=0.181N     P=0.178      P=0.074     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mediastinal                                                                                                          |
|     Hyperplasia Lymphoid                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.8%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     639          ---          ---          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.193N     P=0.286N     P=0.300N     P=0.576N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.101N     P=0.255N     P=0.263N     P=0.307N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.107N     P=0.247N     P=0.252N     P=0.272N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.091N     P=0.267N     P=0.281N     P=0.376N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.127N     P=0.244N     P=0.250N     P=0.314N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.115N     P=0.247N     P=0.247N     P=0.247N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 28
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Dilatation                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     13/50 (26%)  13/49 (27%)  4/49 (8%)    7/45 (16%)  |27/50 (54%)  22/50 (44%)  34/50 (68%)  20/50 (40%)  |
|POLY-3 ADJUSTED (b)|     29.6%        32.2%        10.6%        23.2%       |60.7%        49.4%        74.3%        47.5%        |
|TERMINAL (d)       |     4/20 (20%)   5/16 (31%)   1/15 (7%)    0/0 (0%)    |11/22 (50%)  13/25 (52%)  18/22 (82%)  5/11 (46%)   |
|FIRST INCIDENCE    |     521          572          467          575         |407          450          444          527          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.414      P=0.391      P=0.065N     P=0.166     |P=0.183      P=0.156N     P=0.225      P=0.479      |
|POLY 3             |     P=0.131N     P=0.490      P=0.030N*    P=0.367N    |P=0.260N     P=0.188N     P=0.112      P=0.145N     |
|POLY 1.5           |     P=0.089N     P=0.522      P=0.024N*    P=0.258N    |P=0.209N     P=0.188N     P=0.113      P=0.119N     |
|POLY 6             |     P=0.228N     P=0.448      P=0.044N*    P=0.571N    |P=0.371N     P=0.206N     P=0.106      P=0.214N     |
|LOGISTIC REGRESSION|     P=0.077N     P=0.549      P=0.017N*    P=0.225N    |P=0.216N     P=0.195N     P=0.139      P=0.122N     |
|COCH-ARM / FISHERS |     P=0.056N     P=0.567      P=0.017N*    P=0.160N    |P=0.188N     P=0.212N     P=0.109      P=0.115N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Galactocele                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/49 (0%)    0/49 (0%)    0/45 (0%)   |10/50 (20%)  10/50 (20%)  7/50 (14%)   6/50 (12%)   |
|POLY-3 ADJUSTED (b)|     2.4%         0.0%         0.0%         0.0%        |25.1%        23.4%        16.2%        15.7%        |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |7/22 (32%)   4/25 (16%)   2/22 (9%)    0/11 (0%)    |
|FIRST INCIDENCE    |     642          ---          ---          ---         |598          606          541          541          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.344N     P=0.523N     P=0.523N     P=0.570N    |P=0.395N     P=0.497N     P=0.287N     P=0.550N     |
|POLY 3             |     P=0.280N     P=0.519N     P=0.527N     P=0.578N    |P=0.148N     P=0.531N     P=0.231N     P=0.226N     |
|POLY 1.5           |     P=0.300N     P=0.512N     P=0.518N     P=0.551N    |P=0.135N     P=0.558N     P=0.257N     P=0.210N     |
|POLY 6             |     P=0.254N     P=0.528N     P=0.542N     P=0.623N    |P=0.176N     P=0.492N     P=0.204N     P=0.266N     |
|LOGISTIC REGRESSION|     P=0.306N     P=0.492N     P=0.492N     P=0.514N    |P=0.140N     P=0.564N     P=0.269N     P=0.262N     |
|COCH-ARM / FISHERS |     P=0.317N     P=0.505N     P=0.505N     P=0.526N    |P=0.130N     P=0.598N     P=0.298N     P=0.207N     |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 29
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Hyperplasia Cystic                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/49 (0%)    0/49 (0%)    0/45 (0%)   |0/50 (0%)    2/50 (4%)    2/50 (4%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         4.9%         4.8%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    1/25 (4%)    1/22 (5%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          665          625          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.635N     P=0.264      P=0.254      (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.535N     P=0.247      P=0.251      (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.514N     P=0.244      P=0.246      (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.575N     P=0.251      P=0.256      (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.524N     P=0.246      P=0.241      (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.500N     P=0.247      P=0.247      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/49 (2%)    0/49 (0%)    1/45 (2%)   |8/50 (16%)   7/50 (14%)   9/50 (18%)   2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.6%         0.0%         3.6%        |19.7%        16.8%        21.2%        5.4%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |2/22 (9%)    5/25 (20%)   3/22 (14%)   1/11 (9%)    |
|FIRST INCIDENCE    |     ---          703          ---          660         |597          569          627          553          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.146      P=0.451      (e)          P=0.356     |P=0.205N     P=0.424N     P=0.532      P=0.161N     |
|POLY 3             |     P=0.314      P=0.483      (e)          P=0.425     |P=0.076N     P=0.479N     P=0.539      P=0.060N     |
|POLY 1.5           |     P=0.346      P=0.489      (e)          P=0.450     |P=0.060N     P=0.484N     P=0.526      P=0.051N     |
|POLY 6             |     P=0.268      P=0.476      (e)          P=0.382     |P=0.114N     P=0.479N     P=0.551      P=0.085N     |
|LOGISTIC REGRESSION|     P=0.302      P=0.476      (e)          P=0.447     |P=0.063N     P=0.476N     P=0.536      P=0.054N     |
|COCH-ARM / FISHERS |     P=0.383      P=0.495      (e)          P=0.474     |P=0.051N     P=0.500N     P=0.500      P=0.046N*    |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 30
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery: Fat                                                                                                                   |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/5 (100%)   6/6 (100%)   0/0 (0%)     0/1 (0%)    |5/6 (83%)    5/5 (100%)   2/3 (67%)    3/3 (100%)   |
|POLY-3 ADJUSTED (b)|     100.0%       100.0%       0.0%         0.0%        |90.1%        100.0%       85.1%        100.0%       |
|TERMINAL (d)       |     2/2 (100%)   5/5 (100%)   0/0 (0%)     0/0 (0%)    |1/1 (100%)   3/3 (100%)   1/1 (100%)   1/1 (100%)   |
|FIRST INCIDENCE    |     553          639          ---          ---         |569          564          613          611          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.124N     (e)          (e)          P=0.566N    |P=0.374N     P=0.312N     P=0.176N     P=0.481N     |
|POLY 3             |     (e)          (e)          (e)          P<0.001N**  |P=0.711      P=0.797      P=0.885N     P=0.861      |
|POLY 1.5           |     (e)          (e)          (e)          P<0.001N**  |P=0.615      P=0.658      P=0.750N     P=0.745      |
|POLY 6             |     (e)          (e)          (e)          P=1.000     |P=0.941      P=0.985      P=0.997N     P=0.993      |
|LOGISTIC REGRESSION|     P=0.039N*    (e)          (e)          P=0.205N    |P=0.675      P=0.667      P=0.906      P=0.858      |
|COCH-ARM / FISHERS |     P=0.017N*    (e)          (e)          P=0.167N    |P=0.562      P=0.545      P=0.583N     P=0.667      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     11/50 (22%)  14/50 (28%)  20/50 (40%)  11/50 (22%) |8/50 (16%)   10/50 (20%)  14/50 (28%)  3/50 (6%)    |
|POLY-3 ADJUSTED (b)|     25.4%        33.0%        47.7%        31.3%       |20.0%        23.0%        31.8%        8.1%         |
|TERMINAL (d)       |     2/20 (10%)   3/16 (19%)   6/15 (40%)   0/0 (0%)    |4/22 (18%)   3/25 (12%)   6/22 (27%)   1/11 (9%)    |
|FIRST INCIDENCE    |     603          431          438          337         |609          520          515          590          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.002 **   P=0.194      P=0.013 *    P=0.002 **  |P=0.343N     P=0.480      P=0.153      P=0.321N     |
|POLY 3             |     P=0.225      P=0.294      P=0.024 *    P=0.373     |P=0.149N     P=0.474      P=0.162      P=0.119N     |
|POLY 1.5           |     P=0.369      P=0.308      P=0.028 *    P=0.483     |P=0.116N     P=0.444      P=0.141      P=0.106N     |
|POLY 6             |     P=0.070      P=0.273      P=0.018 *    P=0.203     |P=0.227N     P=0.515      P=0.191      P=0.153N     |
|LOGISTIC REGRESSION|     P=0.513      P=0.339      P=0.033 *    P=0.574     |P=0.106N     P=0.410      P=0.128      P=0.146N     |
|COCH-ARM / FISHERS |     P=0.542      P=0.322      P=0.041 *    P=0.595N    |P=0.099N     P=0.398      P=0.114      P=0.100N     |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 31
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |2/50 (4%)    7/50 (14%)   2/49 (4%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|                                                        |5.0%         16.4%        4.8%         5.5%         |
|TERMINAL (d)       |                                                        |0/22 (0%)    3/25 (12%)   1/22 (5%)    1/11 (9%)    |
|FIRST INCIDENCE    |                                                        |598          520          683          553          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.458N     P=0.111      P=0.669N     P=0.604      |
|POLY 3             |                                                        |P=0.335N     P=0.093      P=0.682N     P=0.661      |
|POLY 1.5           |                                                        |P=0.315N     P=0.088      P=0.687N     P=0.677      |
|POLY 6             |                                                        |P=0.377N     P=0.098      P=0.680N     P=0.626      |
|LOGISTIC REGRESSION|                                                        |P=0.305N     P=0.070      P=0.674      P=0.686      |
|COCH-ARM / FISHERS |                                                        |P=0.308N     P=0.080      P=0.684      P=0.684      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    2/50 (4%)    1/50 (2%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     7.2%         5.2%         2.7%         6.3%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     2/20 (10%)   2/16 (13%)   1/15 (7%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     652          730 (T)      730 (T)      660         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.156      P=0.593N     P=0.402N     P=0.130     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.470N     P=0.536N     P=0.345N     P=0.624N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.440N     P=0.520N     P=0.329N     P=0.565N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.516N     P=0.560N     P=0.373N     P=0.626     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.390      P=0.576N     P=0.391N     P=0.530     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.404N     P=0.500N     P=0.309N     P=0.500N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 32
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas: Acinus                                                                                                                 |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     20/50 (40%)  15/50 (30%)  13/50 (26%)  9/50 (18%)  |10/50 (20%)  11/50 (22%)  8/50 (16%)   6/49 (12%)   |
|POLY-3 ADJUSTED (b)|     45.6%        36.4%        32.1%        25.5%       |24.6%        25.8%        18.7%        16.2%        |
|TERMINAL (d)       |     9/20 (45%)   5/16 (31%)   5/15 (33%)   0/0 (0%)    |4/22 (18%)   8/25 (32%)   3/22 (14%)   1/11 (9%)    |
|FIRST INCIDENCE    |     553          575          502          502         |555          450          515          576          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.234      P=0.455N     P=0.371N     P=0.090     |P=0.430N     P=0.584      P=0.371N     P=0.542N     |
|POLY 3             |     P=0.035N*    P=0.256N     P=0.141N     P=0.048N*   |P=0.166N     P=0.548      P=0.350N     P=0.262N     |
|POLY 1.5           |     P=0.020N*    P=0.232N     P=0.125N     P=0.025N*   |P=0.145N     P=0.534      P=0.366N     P=0.233N     |
|POLY 6             |     P=0.088N     P=0.288N     P=0.177N     P=0.131N    |P=0.212N     P=0.554      P=0.335N     P=0.328N     |
|LOGISTIC REGRESSION|     P=0.026N*    P=0.262N     P=0.139N     P=0.033N*   |P=0.145N     P=0.522      P=0.372N     P=0.265N     |
|COCH-ARM / FISHERS |     P=0.011N*    P=0.201N     P=0.101N     P=0.013N*   |P=0.132N     P=0.500      P=0.398N     P=0.220N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas: Artery                                                                                                                 |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     9.7%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     4/20 (20%)   0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     730 (T)      ---          ---          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.051N     P=0.089N     P=0.099N     P=1.000N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.016N*    P=0.069N     P=0.073N     P=0.104N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.017N*    P=0.065N     P=0.068N     P=0.080N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.014N*    P=0.075N     P=0.083N     P=0.163N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.051N     (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.020N*    P=0.059N     P=0.059N     P=0.059N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 33
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Parathyroid Gland                                                                                                                |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     17/48 (35%)  8/49 (16%)   22/48 (46%)  21/45 (47%) |0/44 (0%)    0/45 (0%)    1/41 (2%)    0/46 (0%)    |
|POLY-3 ADJUSTED (b)|     40.5%        20.6%        57.5%        63.4%       |0.0%         0.0%         2.8%         0.0%         |
|TERMINAL (d)       |     7/20 (35%)   2/16 (13%)   12/15 (80%)  0/0 (0%)    |0/18 (0%)    0/24 (0%)    0/19 (0%)    0/10 (0%)    |
|FIRST INCIDENCE    |     626          596          568          568         |---          ---          515          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.132N     P=0.030 *    P<0.001 **  |P=0.700      (e)          P=0.513      (e)          |
|POLY 3             |     P=0.002 **   P=0.041N*    P=0.086      P=0.032 *   |P=0.655      (e)          P=0.510      (e)          |
|POLY 1.5           |     P=0.006 **   P=0.033N*    P=0.125      P=0.080     |P=0.680      (e)          P=0.501      (e)          |
|POLY 6             |     P<0.001 **   P=0.056N     P=0.045 *    P=0.006 **  |P=0.602      (e)          P=0.519      (e)          |
|LOGISTIC REGRESSION|     P<0.001 **   P=0.052N     P=0.045 *    P=0.002 **  |P=0.621      (e)          P=0.337      (e)          |
|COCH-ARM / FISHERS |     P=0.026 *    P=0.027N*    P=0.203      P=0.186     |P=0.696      (e)          P=0.482      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Parathyroid Gland                                                                                                                |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/48 (4%)    0/49 (0%)    0/48 (0%)    0/45 (0%)   |0/44 (0%)    0/45 (0%)    0/41 (0%)    0/46 (0%)    |
|POLY-3 ADJUSTED (b)|     4.9%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/20 (5%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/18 (0%)    0/24 (0%)    0/19 (0%)    0/10 (0%)    |
|FIRST INCIDENCE    |     668          ---          ---          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.216N     P=0.279N     P=0.299N     P=0.718N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.103N     P=0.253N     P=0.265N     P=0.327N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.111N     P=0.244N     P=0.254N     P=0.290N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.094N     P=0.267N     P=0.284N     P=0.398N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.154N     P=0.256N     P=0.271N     P=0.439N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.119N     P=0.242N     P=0.247N     P=0.264N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 34
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland                                                                                                                  |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |4/50 (8%)    2/50 (4%)    2/50 (4%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.8%         0.0%         0.0%         6.3%        |9.9%         4.8%         4.8%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |1/22 (5%)    0/25 (0%)    1/22 (5%)    0/11 (0%)    |
|FIRST INCIDENCE    |     529          ---          ---          658         |616          611          595          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.228      P=0.275N     P=0.297N     P=0.276     |P=0.071N     P=0.313N     P=0.321N     P=0.115N     |
|POLY 3             |     P=0.473      P=0.257N     P=0.264N     P=0.588     |P=0.052N     P=0.323N     P=0.319N     P=0.074N     |
|POLY 1.5           |     P=0.484      P=0.248N     P=0.253N     P=0.640     |P=0.047N*    P=0.327N     P=0.325N     P=0.066N     |
|POLY 6             |     P=0.463      P=0.269N     P=0.283N     P=0.493     |P=0.062N     P=0.320N     P=0.316N     P=0.092N     |
|LOGISTIC REGRESSION|     P=0.503      P=0.214N     P=0.209N     P=0.703     |P=0.043N*    P=0.345N     P=0.342N     P=0.063N     |
|COCH-ARM / FISHERS |     P=0.500      P=0.247N     P=0.247N     P=0.691N    |P=0.044N*    P=0.339N     P=0.339N     P=0.059N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland                                                                                                                  |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |3/50 (6%)    2/50 (4%)    4/50 (8%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |7.5%         4.8%         9.5%         5.5%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |2/22 (9%)    0/25 (0%)    1/22 (5%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |569          450          515          660          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.529      P=0.467N     P=0.516      P=0.668      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.533N     P=0.474N     P=0.532      P=0.539N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.505N     P=0.483N     P=0.520      P=0.516N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.565      P=0.465N     P=0.543      P=0.582N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.470N     P=0.543N     P=0.505      P=0.541N     |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.479N     P=0.500N     P=0.500      P=0.500N     |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 35
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis                                                                                                   |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     11/50 (22%)  9/50 (18%)   8/50 (16%)   2/50 (4%)   |11/50 (22%)  17/50 (34%)  14/50 (28%)  15/50 (30%)  |
|POLY-3 ADJUSTED (b)|     26.1%        22.7%        20.9%        6.3%        |27.0%        40.3%        32.5%        37.5%        |
|TERMINAL (d)       |     8/20 (40%)   5/16 (31%)   6/15 (40%)   0/0 (0%)    |6/22 (27%)   11/25 (44%)  7/22 (32%)   6/11 (55%)   |
|FIRST INCIDENCE    |     529          575          521          584         |459          606          515          483          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.490      P=0.592      P=0.574N     P=0.387     |P=0.026 *    P=0.221      P=0.366      P=0.035 *    |
|POLY 3             |     P=0.025N*    P=0.459N     P=0.386N     P=0.026N*   |P=0.287      P=0.142      P=0.376      P=0.213      |
|POLY 1.5           |     P=0.013N*    P=0.434N     P=0.354N     P=0.014N*   |P=0.317      P=0.139      P=0.356      P=0.238      |
|POLY 6             |     P=0.068N     P=0.492N     P=0.444N     P=0.068N    |P=0.227      P=0.146      P=0.395      P=0.164      |
|LOGISTIC REGRESSION|     P=0.061N     P=0.507N     P=0.462N     P=0.093N    |P=0.254      P=0.157      P=0.361      P=0.222      |
|COCH-ARM / FISHERS |     P=0.007N**   P=0.402N     P=0.306N     P=0.007N**  |P=0.326      P=0.133      P=0.322      P=0.247      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/50 (10%)   2/50 (4%)    0/49 (0%)    6/50 (12%)  |                                                    |
|POLY-3 ADJUSTED (b)|     12.0%        5.2%         0.0%         18.4%       |                                                    |
|TERMINAL (d)       |     3/20 (15%)   0/16 (0%)    0/15 (0%)    0/0 (0%)    |                                                    |
|FIRST INCIDENCE    |     668          703          ---          638         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.004 **   P=0.322N     P=0.071N     P<0.001 **  |                                                    |
|POLY 3             |     P=0.276      P=0.246N     P=0.042N*    P=0.330     |                                                    |
|POLY 1.5           |     P=0.298      P=0.233N     P=0.038N*    P=0.409     |                                                    |
|POLY 6             |     P=0.247      P=0.267N     P=0.049N*    P=0.210     |                                                    |
|LOGISTIC REGRESSION|     P=0.097      P=0.281N     P=0.057N     P=0.116     |                                                    |
|COCH-ARM / FISHERS |     P=0.331      P=0.218N     P=0.030N*    P=0.500     |                                                    |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 36
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    4/50 (8%)    6/49 (12%)   4/50 (8%)   |                                                    |
|POLY-3 ADJUSTED (b)|     7.2%         10.1%        15.8%        12.0%       |                                                    |
|TERMINAL (d)       |     2/20 (10%)   0/16 (0%)    2/15 (13%)   0/0 (0%)    |                                                    |
|FIRST INCIDENCE    |     642          625          521          467         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.056      P=0.432      P=0.132      P=0.134     |                                                    |
|POLY 3             |     P=0.255      P=0.473      P=0.194      P=0.379     |                                                    |
|POLY 1.5           |     P=0.328      P=0.484      P=0.208      P=0.437     |                                                    |
|POLY 6             |     P=0.150      P=0.461      P=0.171      P=0.282     |                                                    |
|LOGISTIC REGRESSION|     P=0.427      P=0.498      P=0.197      P=0.608     |                                                    |
|COCH-ARM / FISHERS |     P=0.414      P=0.500      P=0.233      P=0.500     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/50 (18%)   15/50 (30%)  8/49 (16%)   12/50 (24%) |                                                    |
|POLY-3 ADJUSTED (b)|     20.1%        34.4%        20.1%        31.3%       |                                                    |
|TERMINAL (d)       |     2/20 (10%)   1/16 (6%)    2/15 (13%)   0/0 (0%)    |                                                    |
|FIRST INCIDENCE    |     521          406          467          409         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.093      P=0.095      P=0.586      P=0.091     |                                                    |
|POLY 3             |     P=0.273      P=0.099      P=0.604N     P=0.177     |                                                    |
|POLY 1.5           |     P=0.357      P=0.107      P=0.571N     P=0.239     |                                                    |
|POLY 6             |     P=0.149      P=0.093      P=0.560      P=0.090     |                                                    |
|LOGISTIC REGRESSION|     P=0.281N     P=0.186      P=0.392N     P=0.301N    |                                                    |
|COCH-ARM / FISHERS |     P=0.452      P=0.121      P=0.518N     P=0.312     |                                                    |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 37
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     16/50 (32%)  18/50 (36%)  13/49 (27%)  15/49 (31%) |                                                    |
|POLY-3 ADJUSTED (b)|     35.3%        40.2%        31.2%        42.3%       |                                                    |
|TERMINAL (d)       |     4/20 (20%)   5/16 (31%)   1/15 (7%)    0/0 (0%)    |                                                    |
|FIRST INCIDENCE    |     521          403          438          467         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.026 *    P=0.265      P=0.571N     P=0.003 **  |                                                    |
|POLY 3             |     P=0.389      P=0.395      P=0.427N     P=0.341     |                                                    |
|POLY 1.5           |     P=0.524      P=0.411      P=0.399N     P=0.482     |                                                    |
|POLY 6             |     P=0.209      P=0.363      P=0.479N     P=0.153     |                                                    |
|LOGISTIC REGRESSION|     P=0.218N     P=0.547      P=0.264N     P=0.516N    |                                                    |
|COCH-ARM / FISHERS |     P=0.389N     P=0.417      P=0.353N     P=0.527N    |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Salivary Glands: Submandibular Gland                                                                                             |
|     Cytoplasmic Alteration                                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    50/50 (100%) 49/50 (98%)  48/48 (100%)|1/50 (2%)    48/48 (100%) 49/49 (100%) 49/49 (100%) |
|POLY-3 ADJUSTED (b)|     9.2%         100.0%       98.0%        100.0%      |2.5%         100.0%       100.0%       100.0%       |
|TERMINAL (d)       |     0/20 (0%)    16/16 (100%) 14/15 (93%)  0/0 (0%)    |0/22 (0%)    25/25 (100%) 22/22 (100%) 11/11 (100%) |
|FIRST INCIDENCE    |     344          403          15           337         |555          347          297          483          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 3             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 1.5           |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 6             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION|     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCH-ARM / FISHERS |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 38
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Seminal Vesicle                                                                                                                  |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    2/50 (4%)    6/50 (12%)  |                                                    |
|POLY-3 ADJUSTED (b)|     0.0%         2.6%         5.3%         18.2%       |                                                    |
|TERMINAL (d)       |     0/20 (0%)    1/16 (6%)    0/15 (0%)    0/0 (0%)    |                                                    |
|FIRST INCIDENCE    |     ---          730 (T)      664          568         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.455      P=0.184      P<0.001 **  |                                                    |
|POLY 3             |     P<0.001 **   P=0.486      P=0.216      P=0.006 **  |                                                    |
|POLY 1.5           |     P<0.001 **   P=0.492      P=0.224      P=0.010 *   |                                                    |
|POLY 6             |     P<0.001 **   P=0.477      P=0.204      P=0.003 **  |                                                    |
|LOGISTIC REGRESSION|     P<0.001 **   P=0.455      P=0.221      P=0.011 *   |                                                    |
|COCH-ARM / FISHERS |     P=0.002 **   P=0.500      P=0.247      P=0.013 *   |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Ulcer                                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.7%         0.0%         0.0%         0.0%        |0.0%         0.0%         2.4%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     564          ---          ---          ---         |---          ---          595          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.132N     P=0.262N     P=0.258N     P=0.286N    |P=0.682      (e)          P=0.509      (e)          |
|POLY 3             |     P=0.100N     P=0.258N     P=0.266N     P=0.311N    |P=0.648      (e)          P=0.513      (e)          |
|POLY 1.5           |     P=0.107N     P=0.249N     P=0.254N     P=0.274N    |P=0.675      (e)          P=0.508      (e)          |
|POLY 6             |     P=0.093N     P=0.273N     P=0.286N     P=0.382N    |P=0.595      (e)          P=0.518      (e)          |
|LOGISTIC REGRESSION|     P=0.088N     P=0.199N     P=0.182N     P=0.153N    |P=0.686      (e)          P=0.474      (e)          |
|COCH-ARM / FISHERS |     P=0.115N     P=0.247N     P=0.247N     P=0.247N    |P=0.694      (e)          P=0.500      (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 39
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Fibrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     8/50 (16%)   11/50 (22%)  12/50 (24%)  12/50 (24%) |3/50 (6%)    3/50 (6%)    5/50 (10%)   12/49 (24%)  |
|POLY-3 ADJUSTED (b)|     19.3%        27.7%        31.1%        35.4%       |7.5%         7.3%         12.0%        32.4%        |
|TERMINAL (d)       |     4/20 (20%)   6/16 (38%)   8/15 (53%)   0/0 (0%)    |1/22 (5%)    1/25 (4%)    4/22 (18%)   6/11 (55%)   |
|FIRST INCIDENCE    |     714          596          522          642         |641          618          690          600          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.156      P=0.063      P<0.001 **  |P<0.001 **   P=0.622N     P=0.376      P<0.001 **   |
|POLY 3             |     P=0.071      P=0.258      P=0.163      P=0.088     |P<0.001 **   P=0.647N     P=0.378      P=0.005 **   |
|POLY 1.5           |     P=0.125      P=0.278      P=0.187      P=0.143     |P<0.001 **   P=0.652N     P=0.371      P=0.007 **   |
|POLY 6             |     P=0.023 *    P=0.235      P=0.128      P=0.033 *   |P<0.001 **   P=0.644N     P=0.382      P=0.002 **   |
|LOGISTIC REGRESSION|     P=0.003 **   P=0.181      P=0.084      P<0.001 **  |P<0.001 **   P=0.653N     P=0.391      P=0.003 **   |
|COCH-ARM / FISHERS |     P=0.216      P=0.306      P=0.227      P=0.227     |P<0.001 **   P=0.661N     P=0.357      P=0.010 *    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hematopoietic Cell Proliferation                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    9/50 (18%)   2/50 (4%)    13/50 (26%) |0/50 (0%)    7/50 (14%)   6/50 (12%)   2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     4.8%         21.4%        5.3%         34.6%       |0.0%         16.3%        14.2%        5.4%         |
|TERMINAL (d)       |     1/20 (5%)    1/16 (6%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    1/25 (4%)    3/22 (14%)   0/11 (0%)    |
|FIRST INCIDENCE    |     729          406          619          409         |---          606          444          534          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.021 *    P=0.623      P<0.001 **  |P=0.343      P=0.015 *    P=0.022 *    P=0.229      |
|POLY 3             |     P<0.001 **   P=0.025 *    P=0.664      P<0.001 **  |P=0.465      P=0.010 *    P=0.019 *    P=0.223      |
|POLY 1.5           |     P=0.002 **   P=0.025 *    P=0.675      P<0.001 **  |P=0.495      P=0.009 **   P=0.018 *    P=0.230      |
|POLY 6             |     P<0.001 **   P=0.025 *    P=0.646      P<0.001 **  |P=0.398      P=0.012 *    P=0.021 *    P=0.208      |
|LOGISTIC REGRESSION|     P=0.015 *    P=0.037 *    P=0.675      P=0.013 *   |P=0.512      P=0.008 **   P=0.018 *    P=0.195      |
|COCH-ARM / FISHERS |     P=0.004 **   P=0.026 *    P=0.691N     P=0.002 **  |P=0.506      P=0.006 **   P=0.013 *    P=0.242      |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 40
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Inflammation Granulomatous                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    2/50 (4%)    1/50 (2%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         4.9%         2.4%         2.8%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    2/25 (8%)    1/22 (5%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          730 (T)      730 (T)      620          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.339      P=0.266      P=0.500      P=0.477      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.469      P=0.245      P=0.510      P=0.485      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.486      P=0.243      P=0.507      P=0.492      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.435      P=0.248      P=0.514      P=0.469      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.446      P=0.266      P=0.500      P=0.492      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.494      P=0.247      P=0.500      P=0.495      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen: Red Pulp                                                                                                                 |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         5.5%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          553          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.032 *    (e)          (e)          P=0.197      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.041 *    (e)          (e)          P=0.221      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.043 *    (e)          (e)          P=0.229      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.039 *    (e)          (e)          P=0.206      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.046 *    (e)          (e)          P=0.229      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.045 *    (e)          (e)          P=0.242      |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 41
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    0/50 (0%)    1/50 (2%)    6/50 (12%)  |0/50 (0%)    0/49 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     7.1%         0.0%         2.7%         18.2%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    1/15 (7%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     588          ---          730 (T)      568         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.002 **   P=0.151N     P=0.400N     P=0.027 *   |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.035 *    P=0.135N     P=0.350N     P=0.134     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.040 *    P=0.128N     P=0.332N     P=0.181     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.028 *    P=0.147N     P=0.382N     P=0.076     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.039 *    P=0.110N     P=0.312N     P=0.222     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.050      P=0.121N     P=0.309N     P=0.243     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Ulcer                                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/50 (14%)   1/50 (2%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    2/49 (4%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     16.7%        2.6%         0.0%         0.0%        |0.0%         4.9%         0.0%         0.0%         |
|TERMINAL (d)       |     3/20 (15%)   1/16 (6%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     639          730 (T)      ---          ---         |---          609          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.014N*    P=0.069N     P=0.032N*    P=0.484N    |P=0.464N     P=0.261      (e)          (e)          |
|POLY 3             |     P<0.001N**   P=0.038N*    P=0.011N*    P=0.022N*   |P=0.403N     P=0.243      (e)          (e)          |
|POLY 1.5           |     P<0.001N**   P=0.035N*    P=0.010N*    P=0.013N*   |P=0.401N     P=0.239      (e)          (e)          |
|POLY 6             |     P<0.001N**   P=0.045N*    P=0.015N*    P=0.053N    |P=0.409N     P=0.248      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.005N**   P=0.048N*    P=0.017N*    P=0.086N    |P=0.404N     P=0.232      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.002N**   P=0.030N*    P=0.006N**   P=0.006N**  |P=0.404N     P=0.242      (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 42
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    14/50 (28%)  32/50 (64%)  37/50 (74%) |3/50 (6%)    41/50 (82%)  45/50 (90%)  39/48 (81%)  |
|POLY-3 ADJUSTED (b)|     0.0%         34.6%        72.3%        81.2%       |7.3%         86.0%        93.2%        84.1%        |
|TERMINAL (d)       |     0/20 (0%)    7/16 (44%)   12/15 (80%)  0/0 (0%)    |0/22 (0%)    21/25 (84%)  20/22 (91%)  8/11 (73%)   |
|FIRST INCIDENCE    |     ---          431          438          337         |407          347          444          508          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 3             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 1.5           |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 6             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION|     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCH-ARM / FISHERS |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Inflammation Focal                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/48 (0%)    |
|POLY-3 ADJUSTED (b)|     4.7%         7.6%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    1/16 (6%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     588          606          ---          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.155N     P=0.439      P=0.277N     P=0.372N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.101N     P=0.468      P=0.265N     P=0.309N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.086N     P=0.482      P=0.253N     P=0.273N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.134N     P=0.449      P=0.284N     P=0.380N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.066N     P=0.523      P=0.211N     P=0.193N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.073N     P=0.500      P=0.247N     P=0.247N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 43
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     10/50 (20%)  4/50 (8%)    15/50 (30%)  14/50 (28%) |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/48 (0%)    |
|POLY-3 ADJUSTED (b)|     23.1%        10.1%        37.7%        39.5%       |0.0%         0.0%         2.4%         0.0%         |
|TERMINAL (d)       |     2/20 (10%)   0/16 (0%)    4/15 (27%)   0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     588          596          568          523         |---          ---          690          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.160N     P=0.058      P<0.001 **  |P=0.662      (e)          P=0.520      (e)          |
|POLY 3             |     P=0.012 *    P=0.097N     P=0.109      P=0.087     |P=0.656      (e)          P=0.511      (e)          |
|POLY 1.5           |     P=0.025 *    P=0.086N     P=0.132      P=0.147     |P=0.677      (e)          P=0.507      (e)          |
|POLY 6             |     P=0.003 **   P=0.118N     P=0.079      P=0.031 *   |P=0.609      (e)          P=0.516      (e)          |
|LOGISTIC REGRESSION|     P=0.015 *    P=0.077N     P=0.126      P=0.124     |P=0.686      (e)          P=0.508      (e)          |
|COCH-ARM / FISHERS |     P=0.055      P=0.074N     P=0.178      P=0.241     |P=0.690      (e)          P=0.500      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Ulcer                                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    2/50 (4%)    3/50 (6%)    2/50 (4%)   |3/50 (6%)    4/50 (8%)    4/50 (8%)    0/48 (0%)    |
|POLY-3 ADJUSTED (b)|     9.3%         5.1%         7.9%         6.3%        |7.5%         9.7%         9.5%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    1/15 (7%)    0/0 (0%)    |1/22 (5%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     521          664          596          658         |598          650          557          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.535      P=0.401N     P=0.571N     P=0.525N    |P=0.179N     P=0.547      P=0.529      P=0.189N     |
|POLY 3             |     P=0.431N     P=0.386N     P=0.569N     P=0.486N    |P=0.123N     P=0.519      P=0.528      P=0.139N     |
|POLY 1.5           |     P=0.377N     P=0.364N     P=0.541N     P=0.413N    |P=0.109N     P=0.513      P=0.518      P=0.130N     |
|POLY 6             |     P=0.526N     P=0.417N     P=0.612N     P=0.609N    |P=0.154N     P=0.526      P=0.537      P=0.159N     |
|LOGISTIC REGRESSION|     P=0.295N     P=0.290N     P=0.442N     P=0.236N    |P=0.105N     P=0.510      P=0.502      P=0.128N     |
|COCH-ARM / FISHERS |     P=0.319N     P=0.339N     P=0.500N     P=0.339N    |P=0.103N     P=0.500      P=0.500      P=0.129N     |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 44
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular: Neuroendocrine Cell                                                                                          |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    8/50 (16%)  |0/50 (0%)    5/50 (10%)   11/50 (22%)  9/48 (19%)   |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         2.7%         24.1%       |0.0%         12.3%        25.6%        22.9%        |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    1/15 (7%)    0/0 (0%)    |0/22 (0%)    5/25 (20%)   5/22 (23%)   1/11 (9%)    |
|FIRST INCIDENCE    |     ---          ---          730 (T)      598         |---          730 (T)      527          508          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   (e)          P=0.443      P<0.001 **  |P<0.001 **   P=0.042 *    P<0.001 **   P=0.002 **   |
|POLY 3             |     P<0.001 **   (e)          P=0.479      P<0.001 **  |P=0.003 **   P=0.033 *    P<0.001 **   P<0.001 **   |
|POLY 1.5           |     P<0.001 **   (e)          P=0.487      P=0.002 **  |P=0.003 **   P=0.032 *    P<0.001 **   P<0.001 **   |
|POLY 6             |     P<0.001 **   (e)          P=0.466      P<0.001 **  |P=0.002 **   P=0.033 *    P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION|     P<0.001 **   (e)          P=0.443      P<0.001 **  |P=0.003 **   P=0.042 *    P<0.001 **   P<0.001 **   |
|COCH-ARM / FISHERS |     P<0.001 **   (e)          P=0.500      P=0.003 **  |P=0.003 **   P=0.028 *    P<0.001 **   P<0.001 **   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes: Germinal Epithelium                                                                                                      |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    1/49 (2%)    0/49 (0%)    3/50 (6%)   |                                                    |
|POLY-3 ADJUSTED (b)|     7.1%         2.6%         0.0%         9.2%        |                                                    |
|TERMINAL (d)       |     1/20 (5%)    1/16 (6%)    0/15 (0%)    0/0 (0%)    |                                                    |
|FIRST INCIDENCE    |     521          730 (T)      ---          502         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.285      P=0.362N     P=0.153N     P=0.409     |                                                    |
|POLY 3             |     P=0.480      P=0.343N     P=0.145N     P=0.538     |                                                    |
|POLY 1.5           |     P=0.501      P=0.330N     P=0.136N     P=0.599     |                                                    |
|POLY 6             |     P=0.449      P=0.363N     P=0.161N     P=0.430     |                                                    |
|LOGISTIC REGRESSION|     P=0.588      P=0.300N     P=0.103N     P=0.525N    |                                                    |
|COCH-ARM / FISHERS |     P=0.528      P=0.316N     P=0.125N     P=0.661N    |                                                    |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 45
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes: Interstitial Cell                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    0/49 (0%)    0/49 (0%)    0/50 (0%)   |                                                    |
|POLY-3 ADJUSTED (b)|     7.0%         0.0%         0.0%         0.0%        |                                                    |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |                                                    |
|FIRST INCIDENCE    |     521          ---          ---          ---         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.065N     P=0.141N     P=0.146N     P=0.191N    |                                                    |
|POLY 3             |     P=0.041N*    P=0.139N     P=0.147N     P=0.184N    |                                                    |
|POLY 1.5           |     P=0.043N*    P=0.132N     P=0.137N     P=0.150N    |                                                    |
|POLY 6             |     P=0.038N*    P=0.151N     P=0.164N     P=0.258N    |                                                    |
|LOGISTIC REGRESSION|     P=0.034N*    P=0.100N     P=0.089N     P=0.067N    |                                                    |
|COCH-ARM / FISHERS |     P=0.048N*    P=0.125N     P=0.125N     P=0.121N    |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     22/50 (44%)  25/50 (50%)  25/50 (50%)  10/48 (21%) |32/50 (64%)  33/49 (67%)  30/49 (61%)  32/50 (64%)  |
|POLY-3 ADJUSTED (b)|     50.8%        58.3%        60.1%        30.3%       |71.4%        73.4%        67.0%        73.1%        |
|TERMINAL (d)       |     14/20 (70%)  12/16 (75%)  13/15 (87%)  0/0 (0%)    |18/22 (82%)  19/25 (76%)  15/22 (68%)  10/11 (91%)  |
|FIRST INCIDENCE    |     610          431          502          502         |407          443          444          534          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.017 *    P=0.111      P=0.062      P=0.011 *   |P=0.016 *    P=0.424N     P=0.374N     P=0.030 *    |
|POLY 3             |     P=0.051N     P=0.308      P=0.250      P=0.051N    |P=0.524      P=0.508      P=0.411N     P=0.523      |
|POLY 1.5           |     P=0.018N*    P=0.324      P=0.281      P=0.025N*   |P=0.512N     P=0.488      P=0.429N     P=0.568      |
|POLY 6             |     P=0.207N     P=0.285      P=0.198      P=0.151N    |P=0.441      P=0.532      P=0.395N     P=0.445      |
|LOGISTIC REGRESSION|     P=0.084N     P=0.232      P=0.165      P=0.209N    |P=0.530      P=0.512      P=0.399N     P=0.530      |
|COCH-ARM / FISHERS |     P=0.006N**   P=0.344      P=0.344      P=0.012N*   |P=0.477N     P=0.445      P=0.469N     P=0.582N     |
|=================================================================================================================================|
       Date:  07/20/98                           EXPERIMENT: 05187 TEST: 09                                            Page 46
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                   METHYLEUGENOL
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder                                                                                                                  |
|     Ulcer                                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/49 (2%)    1/50 (2%)    2/49 (4%)    0/49 (0%)   |0/50 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.4%         2.6%         5.4%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/20 (0%)    0/16 (0%)    0/15 (0%)    0/0 (0%)    |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |     617          660          664          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.631N     P=0.739      P=0.410      P=0.557N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.470N     P=0.747      P=0.463      P=0.559N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.421N     P=0.755      P=0.478      P=0.531N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.569N     P=0.736      P=0.441      P=0.606N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.391N     P=0.742N     P=0.501      P=0.454N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.368N     P=0.747N     P=0.500      P=0.500N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      37 MG/KG     75 MG/KG     150         |0 MG/KG      37 MG/KG     75 MG/KG     150          |
|                   |                                            MG/KG       |                                       MG/KG        |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Hyperplasia Cystic                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |2/50 (4%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|                                                        |5.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |                                                        |0/22 (0%)    0/25 (0%)    0/22 (0%)    0/11 (0%)    |
|FIRST INCIDENCE    |                                                        |549          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.131N     P=0.225N     P=0.235N     P=0.301N     |
|POLY 3             |                                                        |P=0.109N     P=0.231N     P=0.229N     P=0.258N     |
|POLY 1.5           |                                                        |P=0.113N     P=0.233N     P=0.233N     P=0.246N     |
|POLY 6             |                                                        |P=0.102N     P=0.230N     P=0.226N     P=0.284N     |
|LOGISTIC REGRESSION|                                                        |P=0.119N     P=0.247N     P=0.265N     P=0.235N     |
|COCH-ARM / FISHERS |                                                        |P=0.116N     P=0.247N     P=0.253N     P=0.247N     |
|=================================================================================================================================|
(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).