Skip to Main Navigation
Skip to Page Content
Share This:
https://ntp.niehs.nih.gov/go/4794

TDMS Study 88036-04 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                                       ANTHRAQUINONE                                     DATE: 05/27/99       
EXPERIMENT: 88036 TEST: 04                                                                                     TIME: 11:24:29       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-25337                              ROUTE: DOSED FEED                                              NTP C#: C88036       
PATHOLOGIST: RYAN, M.                                                                                          CAS: 84-65-1         
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                      FINAL #2 CORE STUDY MICE                                                      
                                                                                                                                    

               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10   
LAB: Battelle Columbus                                       ANTHRAQUINONE                                     DATE: 05/27/99     
EXPERIMENT: 88036 TEST: 04                                                                                     TIME: 11:24:29     
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                      
CONT: NO1-ES-25337                              ROUTE: DOSED FEED                                              NTP C#: C88036     
PATHOLOGIST: RYAN, M.                                                                                          CAS: 84-65-1       



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

Male Mice
------------
Organ                                 Morphology
-----                                 ----------
Epididymis                             Granuloma Sperm
Heart: Myocardium                      Degeneration
Islets, Pancreatic                     Hyperplasia
Kidney                                 Nephropathy
                                       Pigmentation
Liver                                  Clear Cell Focus
                                       Degeneration Fatty Focal
                                       Eosinophilic Focus
                                       Hematopoietic Cell Proliferation
                                       Mineralization
                                       Necrosis Focal
Liver: Centrilobular                   Hypertrophy
Liver: Hepatocyte                      Erythrophagocytosis
Mesentery: Fat                         Necrosis
Preputial Gland                        Cyst
Seminal Vesicle                        Inflammation Chronic
Spleen                                 Hematopoietic Cell Proliferation
Stomach, Forestomach: Epithelium       Hyperplasia Focal
Testes: Germinal Epithelium            Degeneration
Thyroid Gland: Follicular Cell         Hyperplasia
Urinary Bladder: Transitional Epithelium
                                       Inclusion Body Intracytoplasmic
===============================================================
Female Mice
------------
Organ                                  Morphology
-----                                  ----------
Heart: Myocardium                      Mineralization
Islets, Pancreatic                     Hyperplasia
Liver                                  Degeneration Fatty Focal
                                       Eosinophilic Focus
                                       Infiltration Cellular Lymphocyte
Liver: Centrilobular                   Hypertrophy
Ovary                                  Angiectasis
Spleen                                 Hematopoietic Cell Proliferation
Urinary Bladder: Transitional Epithelium
                                       Inclusion Body Intracytoplasmic
Uterus: Endometrium                    Hyperplasia Cystic
===============================================================
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 1
                     Statistical Analysis of Non-neoplastic Lesions in        Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/50 (14%)   8/50 (16%)   8/50 (16%)   5/50 (10%)  |0/50 (0%)    1/50 (2%)    1/50 (2%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     14.6%        16.9%        16.9%        12.4%       |0.0%         2.1%         2.2%         4.4%         |
|TERMINAL (d)       |     7/45 (16%)   6/41 (15%)   8/43 (19%)   4/23 (17%)  |0/35 (0%)    1/42 (2%)    0/35 (0%)    2/42 (5%)    |
|FIRST INCIDENCE    |     729 (T)      657          729 (T)      570         |---          730 (T)      700          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.407      P=0.430      P=0.462      P=0.421     |P=0.221      P=0.536      P=0.490      P=0.279      |
|POLY 3             |     P=0.400N     P=0.488      P=0.488      P=0.505N    |P=0.193      P=0.508      P=0.500      P=0.239      |
|POLY 1.5           |     P=0.332N     P=0.499      P=0.498      P=0.443N    |P=0.188      P=0.505      P=0.501      P=0.234      |
|POLY 6             |     P=0.499N     P=0.476      P=0.481      P=0.594N    |P=0.200      P=0.512      P=0.499      P=0.246      |
|LOGISTIC REGRESSION|     P=0.456N     P=0.488      P=0.462      P=0.608N    |P=0.198      P=0.536      P=0.500      P=0.279      |
|COCH-ARM / FISHERS |     P=0.260N     P=0.500      P=0.500      P=0.380N    |P=0.187      P=0.500      P=0.500      P=0.242      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/49 (4%)    0/50 (0%)    0/50 (0%)    0/49 (0%)   |0/50 (0%)    0/50 (0%)    0/49 (0%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     4.3%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         2.2%         |
|TERMINAL (d)       |     2/44 (5%)    0/41 (0%)    0/43 (0%)    0/23 (0%)   |0/35 (0%)    0/42 (0%)    0/35 (0%)    1/42 (2%)    |
|FIRST INCIDENCE    |     729 (T)      ---          ---          ---         |---          ---          ---          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.318N     P=0.254N     P=0.244N     P=0.390N    |P=0.234      (e)          (e)          P=0.536      |
|POLY 3             |     P=0.235N     P=0.238N     P=0.236N     P=0.278N    |P=0.214      (e)          (e)          P=0.501      |
|POLY 1.5           |     P=0.238N     P=0.234N     P=0.233N     P=0.257N    |P=0.212      (e)          (e)          P=0.497      |
|POLY 6             |     P=0.228N     P=0.243N     P=0.238N     P=0.310N    |P=0.218      (e)          (e)          P=0.508      |
|LOGISTIC REGRESSION|     P=0.318N     (e)          (e)          (e)         |(e)          (e)          (e)          P=0.536      |
|COCH-ARM / FISHERS |     P=0.239N     P=0.242N     P=0.242N     P=0.247N    |P=0.212      (e)          (e)          P=0.495      |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 2
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Blood Vessel: Aorta                                                                                                              |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    1/49 (2%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |4.3%         0.0%         2.3%         0.0%         |
|TERMINAL (d)       |     0/45 (0%)    0/41 (0%)    0/42 (0%)    0/23 (0%)   |0/35 (0%)    0/42 (0%)    0/34 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |242          ---          589          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.272N     P=0.240N     P=0.497N     P=0.249N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.272N     P=0.236N     P=0.516N     P=0.244N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.274N     P=0.237N     P=0.513N     P=0.246N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.270N     P=0.234N     P=0.522N     P=0.238N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.076N     P=0.319N     P=0.700N     P=0.096N     |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.270N     P=0.247N     P=0.508N     P=0.253N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Fibrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/50 (4%)    2/50 (4%)    1/50 (2%)    3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |4.5%         4.3%         2.2%         6.7%         |
|TERMINAL (d)       |     0/45 (0%)    0/41 (0%)    0/43 (0%)    0/23 (0%)   |2/35 (6%)    2/42 (5%)    1/35 (3%)    3/42 (7%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |730 (T)      730 (T)      730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.431      P=0.628N     P=0.500N     P=0.583      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.374      P=0.679N     P=0.500N     P=0.503      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.367      P=0.684N     P=0.498N     P=0.494      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.385      P=0.673N     P=0.504N     P=0.518      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.431      P=0.628N     P=0.500N     P=0.583      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.369      P=0.691N     P=0.500N     P=0.490      |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 3
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Epididymis                                                                                                                       |
|     Granuloma Sperm                                                                                                             |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    3/50 (6%)   |                                                    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         7.3%        |                                                    |
|TERMINAL (d)       |     0/45 (0%)    0/41 (0%)    0/43 (0%)    1/23 (4%)   |                                                    |
|FIRST INCIDENCE    |     ---          ---          ---          554         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.004 **   (e)          (e)          P=0.080     |                                                    |
|POLY 3             |     P=0.006 **   (e)          (e)          P=0.093     |                                                    |
|POLY 1.5           |     P=0.007 **   (e)          (e)          P=0.105     |                                                    |
|POLY 6             |     P=0.005 **   (e)          (e)          P=0.078     |                                                    |
|LOGISTIC REGRESSION|     P=0.012 *    (e)          (e)          P=0.127     |                                                    |
|COCH-ARM / FISHERS |     P=0.009 **   (e)          (e)          P=0.121     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart: Atrium                                                                                                                    |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|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%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     4.2%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/45 (2%)    0/41 (0%)    0/43 (0%)    0/23 (0%)   |0/35 (0%)    0/42 (0%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     702          ---          ---          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.316N     P=0.263N     P=0.250N     P=0.386N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.234N     P=0.244N     P=0.241N     P=0.282N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.237N     P=0.239N     P=0.238N     P=0.259N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.226N     P=0.249N     P=0.243N     P=0.316N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.254N     P=0.238N     P=0.238N     P=0.295N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.238N     P=0.247N     P=0.247N     P=0.247N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 4
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart: Myocardium                                                                                                                |
|     Degeneration                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    0/50 (0%)    3/50 (6%)    5/50 (10%)  |2/50 (4%)    0/50 (0%)    1/50 (2%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     8.3%         0.0%         6.3%         12.2%       |4.5%         0.0%         2.2%         2.2%         |
|TERMINAL (d)       |     4/45 (9%)    0/41 (0%)    3/43 (7%)    2/23 (9%)   |1/35 (3%)    0/42 (0%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      570         |717          ---          491          549          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.028 *    P=0.076N     P=0.525N     P=0.200     |P=0.604N     P=0.209N     P=0.507N     P=0.470N     |
|POLY 3             |     P=0.111      P=0.064N     P=0.508N     P=0.401     |P=0.621N     P=0.229N     P=0.495N     P=0.494N     |
|POLY 1.5           |     P=0.128      P=0.062N     P=0.501N     P=0.450     |P=0.624N     P=0.232N     P=0.495N     P=0.503N     |
|POLY 6             |     P=0.090      P=0.067N     P=0.512N     P=0.336     |P=0.616N     P=0.225N     P=0.498N     P=0.481N     |
|LOGISTIC REGRESSION|     P=0.138      (e)          P=0.525N     P=0.483     |P=0.548N     P=0.223N     P=0.537N     P=0.501N     |
|COCH-ARM / FISHERS |     P=0.153      P=0.059N     P=0.500N     P=0.500     |P=0.621N     P=0.247N     P=0.500N     P=0.508N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart: Myocardium                                                                                                                |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    1/50 (2%)   |2/50 (4%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         2.1%         2.5%        |4.3%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/45 (0%)    0/41 (0%)    0/43 (0%)    0/23 (0%)   |0/35 (0%)    0/42 (0%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     ---          ---          685          569         |242          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.247      (e)          P=0.496      P=0.483     |P=0.245N     P=0.240N     P=0.242N     P=0.249N     |
|POLY 3             |     P=0.255      (e)          P=0.498      P=0.465     |P=0.240N     P=0.236N     P=0.245N     P=0.244N     |
|POLY 1.5           |     P=0.279      (e)          P=0.500      P=0.482     |P=0.240N     P=0.237N     P=0.242N     P=0.246N     |
|POLY 6             |     P=0.222      (e)          P=0.497      P=0.442     |P=0.240N     P=0.234N     P=0.250N     P=0.238N     |
|LOGISTIC REGRESSION|     P=0.325      (e)          P=0.494      P=0.492     |P=0.048N*    P=0.319N     P=0.321N     P=0.096N     |
|COCH-ARM / FISHERS |     P=0.305      (e)          P=0.500      P=0.500     |P=0.241N     P=0.247N     P=0.247N     P=0.253N     |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 5
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     40/50 (80%)  40/50 (80%)  29/50 (58%)  17/42 (40%) |6/50 (12%)   13/50 (26%)  10/50 (20%)  14/49 (29%)  |
|POLY-3 ADJUSTED (b)|     80.0%        82.4%        60.9%        44.2%       |13.4%        27.8%        22.3%        30.8%        |
|TERMINAL (d)       |     35/45 (78%)  35/41 (85%)  27/43 (63%)  10/23 (44%) |6/35 (17%)   12/42 (29%)  10/35 (29%)  13/42 (31%)  |
|FIRST INCIDENCE    |     15           456          662          497         |730 (T)      703          730 (T)      625          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.050N     P=0.302      P=0.046N*    P=0.133N    |P=0.168      P=0.131      P=0.198      P=0.091      |
|POLY 3             |     P<0.001N**   P=0.482      P=0.029N*    P<0.001N**  |P=0.094      P=0.073      P=0.203      P=0.039 *    |
|POLY 1.5           |     P<0.001N**   P=0.530      P=0.022N*    P<0.001N**  |P=0.085      P=0.069      P=0.208      P=0.034 *    |
|POLY 6             |     P<0.001N**   P=0.418      P=0.038N*    P<0.001N**  |P=0.113      P=0.079      P=0.194      P=0.048 *    |
|LOGISTIC REGRESSION|     P<0.001N**   P=0.598N     P=0.015N*    P<0.001N**  |P=0.121      P=0.094      P=0.198      P=0.048 *    |
|COCH-ARM / FISHERS |     P<0.001N**   P=0.598N     P=0.015N*    P<0.001N**  |P=0.087      P=0.062      P=0.207      P=0.035 *    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Infarct                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/49 (0%)    0/49 (0%)    0/47 (0%)   |0/49 (0%)    2/50 (4%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     2.1%         0.0%         0.0%         0.0%        |0.0%         4.3%         0.0%         0.0%         |
|TERMINAL (d)       |     0/45 (0%)    0/40 (0%)    0/42 (0%)    0/23 (0%)   |0/35 (0%)    2/42 (5%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     550          ---          ---          ---         |---          730 (T)      ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.480N     P=0.504N     P=0.508N     P=0.513N    |P=0.359N     P=0.279      (e)          (e)          |
|POLY 3             |     P=0.465N     P=0.512N     P=0.509N     P=0.549N    |P=0.373N     P=0.249      (e)          (e)          |
|POLY 1.5           |     P=0.474N     P=0.507N     P=0.506N     P=0.532N    |P=0.377N     P=0.247      (e)          (e)          |
|POLY 6             |     P=0.449N     P=0.518N     P=0.512N     P=0.574N    |P=0.366N     P=0.252      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.497N     P=0.574N     P=0.574N     P=0.531N    |(e)          P=0.279      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.480N     P=0.505N     P=0.505N     P=0.515N    |P=0.382N     P=0.253      (e)          (e)          |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 6
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Nephropathy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     29/50 (58%)  25/49 (51%)  27/49 (55%)  18/47 (38%) |4/49 (8%)    3/50 (6%)    3/49 (6%)    7/49 (14%)   |
|POLY-3 ADJUSTED (b)|     60.3%        54.1%        58.2%        46.4%       |8.9%         6.4%         6.8%         15.4%        |
|TERMINAL (d)       |     28/45 (62%)  23/40 (58%)  25/42 (60%)  14/23 (61%) |3/35 (9%)    2/42 (5%)    2/35 (6%)    6/42 (14%)   |
|FIRST INCIDENCE    |     702          657          711          590         |554          703          700          625          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.195      P=0.509N     P=0.570N     P=0.264     |P=0.154      P=0.424N     P=0.506N     P=0.356      |
|POLY 3             |     P=0.148N     P=0.343N     P=0.500N     P=0.136N    |P=0.110      P=0.476N     P=0.504N     P=0.270      |
|POLY 1.5           |     P=0.078N     P=0.315N     P=0.472N     P=0.073N    |P=0.106      P=0.480N     P=0.499N     P=0.261      |
|POLY 6             |     P=0.301N     P=0.378N     P=0.523N     P=0.281N    |P=0.117      P=0.471N     P=0.513N     P=0.286      |
|LOGISTIC REGRESSION|     P=0.544      P=0.442N     P=0.533N     P=0.564N    |P=0.107      P=0.492N     P=0.499N     P=0.261      |
|COCH-ARM / FISHERS |     P=0.037N*    P=0.310N     P=0.465N     P=0.041N*   |P=0.109      P=0.489N     P=0.500N     P=0.262      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Pigmentation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    2/49 (4%)    2/49 (4%)    18/47 (38%) |1/49 (2%)    0/50 (0%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         4.3%         4.2%         43.3%       |2.3%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/45 (0%)    1/40 (3%)    0/42 (0%)    6/23 (26%)  |0/35 (0%)    0/42 (0%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     ---          658          481          554         |690          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.222      P=0.237      P<0.001 **  |P=0.468N     P=0.486N     P=0.515N     P=0.490N     |
|POLY 3             |     P<0.001 **   P=0.228      P=0.234      P<0.001 **  |P=0.477N     P=0.490N     P=0.500N     P=0.497N     |
|POLY 1.5           |     P<0.001 **   P=0.232      P=0.235      P<0.001 **  |P=0.476N     P=0.492N     P=0.499N     P=0.500N     |
|POLY 6             |     P<0.001 **   P=0.224      P=0.233      P<0.001 **  |P=0.478N     P=0.488N     P=0.503N     P=0.492N     |
|LOGISTIC REGRESSION|     P<0.001 **   P=0.230      P=0.170      P<0.001 **  |P=0.470N     P=0.503N     P=0.502N     P=0.500N     |
|COCH-ARM / FISHERS |     P<0.001 **   P=0.242      P=0.242      P<0.001 **  |P=0.473N     P=0.495N     P=0.500N     P=0.500N     |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 7
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/49 (0%)    0/49 (0%)    0/47 (0%)   |0/49 (0%)    0/50 (0%)    0/49 (0%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     4.2%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         2.2%         |
|TERMINAL (d)       |     2/45 (4%)    0/40 (0%)    0/42 (0%)    0/23 (0%)   |0/35 (0%)    0/42 (0%)    0/35 (0%)    1/42 (2%)    |
|FIRST INCIDENCE    |     729 (T)      ---          ---          ---         |---          ---          ---          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.321N     P=0.265N     P=0.254N     P=0.395N    |P=0.234      (e)          (e)          P=0.536      |
|POLY 3             |     P=0.241N     P=0.248N     P=0.245N     P=0.294N    |P=0.215      (e)          (e)          P=0.504      |
|POLY 1.5           |     P=0.244N     P=0.244N     P=0.243N     P=0.272N    |P=0.213      (e)          (e)          P=0.501      |
|POLY 6             |     P=0.234N     P=0.253N     P=0.247N     P=0.325N    |P=0.218      (e)          (e)          P=0.510      |
|LOGISTIC REGRESSION|     P=0.321N     (e)          (e)          (e)         |(e)          (e)          (e)          P=0.536      |
|COCH-ARM / FISHERS |     P=0.246N     P=0.253N     P=0.253N     P=0.263N    |P=0.214      (e)          (e)          P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Basophilic Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    3/50 (6%)    1/50 (2%)    0/49 (0%)   |1/49 (2%)    1/50 (2%)    0/50 (0%)    3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     0.0%         6.4%         2.1%         0.0%        |2.3%         2.1%         0.0%         6.6%         |
|TERMINAL (d)       |     0/45 (0%)    2/41 (5%)    1/43 (2%)    0/23 (0%)   |1/35 (3%)    1/42 (2%)    0/35 (0%)    2/42 (5%)    |
|FIRST INCIDENCE    |     ---          658          729 (T)      ---         |730 (T)      730 (T)      ---          681          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.424N     P=0.110      P=0.491      (e)         |P=0.155      P=0.721N     P=0.500N     P=0.363      |
|POLY 3             |     P=0.338N     P=0.115      P=0.497      (e)         |P=0.127      P=0.749N     P=0.497N     P=0.314      |
|POLY 1.5           |     P=0.312N     P=0.118      P=0.500      (e)         |P=0.124      P=0.751N     P=0.496N     P=0.307      |
|POLY 6             |     P=0.376N     P=0.112      P=0.495      (e)         |P=0.131      P=0.745N     P=0.501N     P=0.326      |
|LOGISTIC REGRESSION|     P=0.306N     P=0.120      P=0.491      (e)         |P=0.130      P=0.721N     (e)          P=0.311      |
|COCH-ARM / FISHERS |     P=0.286N     P=0.121      P=0.500      (e)         |P=0.125      P=0.747N     P=0.495N     P=0.309      |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 8
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Clear Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     14/50 (28%)  12/50 (24%)  9/50 (18%)   2/49 (4%)   |4/49 (8%)    1/50 (2%)    1/50 (2%)    3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     29.2%        25.5%        19.0%        5.1%        |8.9%         2.1%         2.2%         6.5%         |
|TERMINAL (d)       |     14/45 (31%)  11/41 (27%)  9/43 (21%)   1/23 (4%)   |3/35 (9%)    1/42 (2%)    0/35 (0%)    2/42 (5%)    |
|FIRST INCIDENCE    |     729 (T)      666          729 (T)      690         |554          730 (T)      589          477          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.023N*    P=0.518N     P=0.201N     P=0.042N*   |P=0.580      P=0.142N     P=0.181N     P=0.435N     |
|POLY 3             |     P=0.003N**   P=0.434N     P=0.179N     P=0.003N**  |P=0.548      P=0.166N     P=0.175N     P=0.487N     |
|POLY 1.5           |     P=0.002N**   P=0.416N     P=0.172N     P=0.002N**  |P=0.542      P=0.168N     P=0.173N     P=0.497N     |
|POLY 6             |     P=0.006N**   P=0.455N     P=0.185N     P=0.008N**  |P=0.557      P=0.164N     P=0.180N     P=0.473N     |
|LOGISTIC REGRESSION|     P=0.011N*    P=0.489N     P=0.201N     P=0.024N*   |P=0.580      P=0.178N     P=0.184N     P=0.491N     |
|COCH-ARM / FISHERS |     P<0.001N**   P=0.410N     P=0.171N     P<0.001N**  |P=0.544      P=0.175N     P=0.175N     P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Degeneration Fatty Focal                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    7/50 (14%)   6/50 (12%)   0/49 (0%)   |2/49 (4%)    3/50 (6%)    1/50 (2%)    9/49 (18%)   |
|POLY-3 ADJUSTED (b)|     0.0%         14.7%        12.7%        0.0%        |4.5%         6.4%         2.2%         19.6%        |
|TERMINAL (d)       |     0/45 (0%)    5/41 (12%)   6/43 (14%)   0/23 (0%)   |1/35 (3%)    3/42 (7%)    0/35 (0%)    7/42 (17%)   |
|FIRST INCIDENCE    |     ---          456          729 (T)      ---         |554          730 (T)      676          549          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.312N     P=0.008 **   P=0.015 *    (e)         |P=0.006 **   P=0.564      P=0.506N     P=0.049 *    |
|POLY 3             |     P=0.210N     P=0.007 **   P=0.015 *    (e)         |P=0.003 **   P=0.519      P=0.498N     P=0.027 *    |
|POLY 1.5           |     P=0.161N     P=0.008 **   P=0.015 *    (e)         |P=0.003 **   P=0.516      P=0.494N     P=0.025 *    |
|POLY 6             |     P=0.292N     P=0.007 **   P=0.014 *    (e)         |P=0.003 **   P=0.522      P=0.505N     P=0.031 *    |
|LOGISTIC REGRESSION|     P=0.126N     P=0.008 **   P=0.015 *    (e)         |P=0.003 **   P=0.500      P=0.521N     P=0.027 *    |
|COCH-ARM / FISHERS |     P=0.126N     P=0.006 **   P=0.013 *    (e)         |P=0.003 **   P=0.510      P=0.492N     P=0.025 *    |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 9
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Eosinophilic Focus                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     14/50 (28%)  17/50 (34%)  24/50 (48%)  20/49 (41%) |6/49 (12%)   15/50 (30%)  11/50 (22%)  22/49 (45%)  |
|POLY-3 ADJUSTED (b)|     29.2%        35.6%        49.6%        48.6%       |13.6%        32.2%        24.5%        48.0%        |
|TERMINAL (d)       |     14/45 (31%)  13/41 (32%)  22/43 (51%)  12/23 (52%) |5/35 (14%)   15/42 (36%)  10/35 (29%)  20/42 (48%)  |
|FIRST INCIDENCE    |     729 (T)      657          453          590         |717          730 (T)      676          549          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.239      P=0.021 *    P<0.001 **  |P=0.004 **   P=0.062      P=0.138      P=0.002 **   |
|POLY 3             |     P=0.042 *    P=0.325      P=0.030 *    P=0.045 *   |P<0.001 **   P=0.029 *    P=0.148      P<0.001 **   |
|POLY 1.5           |     P=0.081      P=0.336      P=0.032 *    P=0.078     |P<0.001 **   P=0.028 *    P=0.153      P<0.001 **   |
|POLY 6             |     P=0.016 *    P=0.317      P=0.029 *    P=0.019 *   |P<0.001 **   P=0.031 *    P=0.139      P<0.001 **   |
|LOGISTIC REGRESSION|     P=0.033 *    P=0.308      P=0.030 *    P=0.011 *   |P<0.001 **   P=0.044 *    P=0.123      P<0.001 **   |
|COCH-ARM / FISHERS |     P=0.152      P=0.333      P=0.032 *    P=0.129     |P<0.001 **   P=0.027 *    P=0.154      P<0.001 **   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Fatty Change Focal                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    1/49 (2%)   |5/49 (10%)   2/50 (4%)    1/50 (2%)    3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     2.1%         0.0%         0.0%         2.5%        |11.3%        4.3%         2.2%         6.7%         |
|TERMINAL (d)       |     1/45 (2%)    0/41 (0%)    0/43 (0%)    0/23 (0%)   |5/35 (14%)   2/42 (5%)    0/35 (0%)    3/42 (7%)    |
|FIRST INCIDENCE    |     729 (T)      ---          ---          702         |730 (T)      730 (T)      676          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.412      P=0.519N     P=0.509N     P=0.614     |P=0.417N     P=0.149N     P=0.107N     P=0.260N     |
|POLY 3             |     P=0.507      P=0.505N     P=0.503N     P=0.715     |P=0.480N     P=0.195N     P=0.097N     P=0.345N     |
|POLY 1.5           |     P=0.520      P=0.502N     P=0.500N     P=0.736     |P=0.484N     P=0.199N     P=0.096N     P=0.355N     |
|POLY 6             |     P=0.491      P=0.510N     P=0.505N     P=0.684     |P=0.472N     P=0.189N     P=0.099N     P=0.330N     |
|LOGISTIC REGRESSION|     P=0.496      (e)          (e)          P=0.705     |P=0.454N     P=0.149N     P=0.104N     P=0.260N     |
|COCH-ARM / FISHERS |     P=0.536      P=0.500N     P=0.500N     P=0.747     |P=0.478N     P=0.210N     P=0.098N     P=0.357N     |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 10
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hematopoietic Cell Proliferation                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    0/50 (0%)    4/49 (8%)   |1/49 (2%)    1/50 (2%)    3/50 (6%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         4.3%         0.0%         10.0%       |2.3%         2.1%         6.5%         2.2%         |
|TERMINAL (d)       |     0/45 (0%)    2/41 (5%)    0/43 (0%)    1/23 (4%)   |0/35 (0%)    0/42 (0%)    1/35 (3%)    1/42 (2%)    |
|FIRST INCIDENCE    |     ---          729 (T)      ---          569         |717          648          491          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.005 **   P=0.218      (e)          P=0.021 *   |P=0.593N     P=0.741N     P=0.307      P=0.729N     |
|POLY 3             |     P=0.022 *    P=0.232      (e)          P=0.041 *   |P=0.619N     P=0.747N     P=0.318      P=0.756N     |
|POLY 1.5           |     P=0.025 *    P=0.236      (e)          P=0.049 *   |P=0.624N     P=0.750N     P=0.318      P=0.760N     |
|POLY 6             |     P=0.018 *    P=0.227      (e)          P=0.032 *   |P=0.610N     P=0.743N     P=0.315      P=0.750N     |
|LOGISTIC REGRESSION|     P=0.033 *    P=0.218      (e)          P=0.065     |P=0.580N     P=0.757      P=0.268      P=0.753N     |
|COCH-ARM / FISHERS |     P=0.031 *    P=0.247      (e)          P=0.056     |P=0.621N     P=0.747N     P=0.316      P=0.753N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Infiltration Cellular Lymphocyte                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         6.7%         |
|TERMINAL (d)       |     0/45 (0%)    0/41 (0%)    0/43 (0%)    0/23 (0%)   |0/35 (0%)    0/42 (0%)    0/35 (0%)    3/42 (7%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.013 *    (e)          (e)          P=0.155      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.008 **   (e)          (e)          P=0.122      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.008 **   (e)          (e)          P=0.119      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.008 **   (e)          (e)          P=0.127      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          P=0.155      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.008 **   (e)          (e)          P=0.121      |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 11
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    2/49 (4%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         4.9%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/45 (0%)    0/41 (0%)    0/43 (0%)    0/23 (0%)   |0/35 (0%)    0/42 (0%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          554         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.037 *    (e)          (e)          P=0.223     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.033 *    (e)          (e)          P=0.201     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.036 *    (e)          (e)          P=0.216     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.030 *    (e)          (e)          P=0.181     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.037 *    (e)          (e)          P=0.212     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.040 *    (e)          (e)          P=0.242     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Mixed Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    2/50 (4%)    4/50 (8%)    1/49 (2%)   |4/49 (8%)    2/50 (4%)    2/50 (4%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     6.3%         4.3%         8.5%         2.5%        |8.9%         4.3%         4.5%         4.4%         |
|TERMINAL (d)       |     3/45 (7%)    2/41 (5%)    4/43 (9%)    0/23 (0%)   |3/35 (9%)    2/42 (5%)    2/35 (6%)    2/42 (5%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      621         |554          730 (T)      730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.530N     P=0.542N     P=0.475      P=0.516N    |P=0.329N     P=0.273N     P=0.338N     P=0.274N     |
|POLY 3             |     P=0.360N     P=0.512N     P=0.492      P=0.376N    |P=0.378N     P=0.318N     P=0.337N     P=0.334N     |
|POLY 1.5           |     P=0.322N     P=0.503N     P=0.499      P=0.344N    |P=0.383N     P=0.321N     P=0.331N     P=0.340N     |
|POLY 6             |     P=0.415N     P=0.522N     P=0.488      P=0.422N    |P=0.370N     P=0.315N     P=0.347N     P=0.323N     |
|LOGISTIC REGRESSION|     P=0.374N     P=0.542N     P=0.475      P=0.336N    |P=0.376N     P=0.329N     P=0.327N     P=0.337N     |
|COCH-ARM / FISHERS |     P=0.281N     P=0.500N     P=0.500      P=0.316N    |P=0.376N     P=0.329N     P=0.329N     P=0.339N     |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 12
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Necrosis Focal                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    3/50 (6%)    8/49 (16%)  |5/49 (10%)   3/50 (6%)    1/50 (2%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     4.2%         6.3%         6.2%         19.4%       |11.3%        6.4%         2.2%         2.2%         |
|TERMINAL (d)       |     1/45 (2%)    2/41 (5%)    1/43 (2%)    2/23 (9%)   |3/35 (9%)    2/42 (5%)    0/35 (0%)    1/42 (2%)    |
|FIRST INCIDENCE    |     710          464          481          497         |690          611          700          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.467      P=0.490      P=0.008 **  |P=0.080N     P=0.288N     P=0.117N     P=0.077N     |
|POLY 3             |     P=0.007 **   P=0.495      P=0.500      P=0.025 *   |P=0.090N     P=0.325N     P=0.098N     P=0.098N     |
|POLY 1.5           |     P=0.010 *    P=0.501      P=0.503      P=0.032 *   |P=0.091N     P=0.332N     P=0.097N     P=0.101N     |
|POLY 6             |     P=0.005 **   P=0.486      P=0.498      P=0.016 *   |P=0.087N     P=0.317N     P=0.102N     P=0.092N     |
|LOGISTIC REGRESSION|     P=0.025 *    P=0.481      P=0.479      P=0.053     |P=0.090N     P=0.338N     P=0.101N     P=0.094N     |
|COCH-ARM / FISHERS |     P=0.014 *    P=0.500      P=0.500      P=0.043 *   |P=0.090N     P=0.346N     P=0.098N     P=0.102N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Bile Duct                                                                                                                 |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    0/50 (0%)    1/49 (2%)   |3/49 (6%)    2/50 (4%)    2/50 (4%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     2.1%         4.3%         0.0%         2.5%        |6.8%         4.3%         4.5%         0.0%         |
|TERMINAL (d)       |     0/45 (0%)    2/41 (5%)    0/43 (0%)    1/23 (4%)   |3/35 (9%)    2/42 (5%)    2/35 (6%)    0/42 (0%)    |
|FIRST INCIDENCE    |     550          729 (T)      ---          729 (T)     |730 (T)      730 (T)      730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.663      P=0.476      P=0.508N     P=0.680     |P=0.083N     P=0.417N     P=0.500N     P=0.091N     |
|POLY 3             |     P=0.595N     P=0.487      P=0.505N     P=0.711     |P=0.098N     P=0.476N     P=0.494N     P=0.115N     |
|POLY 1.5           |     P=0.582N     P=0.495      P=0.502N     P=0.734     |P=0.100N     P=0.480N     P=0.490N     P=0.118N     |
|POLY 6             |     P=0.610N     P=0.477      P=0.508N     P=0.678     |P=0.094N     P=0.469N     P=0.502N     P=0.110N     |
|LOGISTIC REGRESSION|     P=0.543N     P=0.483      P=0.571N     P=0.755N    |P=0.083N     P=0.417N     P=0.500N     (e)          |
|COCH-ARM / FISHERS |     P=0.564N     P=0.500      P=0.500N     P=0.747     |P=0.098N     P=0.490N     P=0.490N     P=0.121N     |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 13
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Centrilobular                                                                                                             |
|     Hypertrophy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     24/50 (48%)  34/50 (68%)  41/50 (82%)  33/49 (67%) |1/49 (2%)    27/50 (54%)  22/50 (44%)  39/49 (80%)  |
|POLY-3 ADJUSTED (b)|     49.3%        70.4%        86.0%        76.6%       |2.3%         57.9%        48.7%        82.6%        |
|TERMINAL (d)       |     22/45 (49%)  30/41 (73%)  38/43 (88%)  22/23 (96%) |1/35 (3%)    27/42 (64%)  21/35 (60%)  35/42 (83%)  |
|FIRST INCIDENCE    |     550          464          662          497         |730 (T)      730 (T)      626          172          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.013 *    P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 3             |     P=0.012 *    P=0.025 *    P<0.001 **   P=0.004 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 1.5           |     P=0.044 *    P=0.031 *    P<0.001 **   P=0.014 *   |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 6             |     P<0.001 **   P=0.020 *    P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION|     P=0.007 **   P=0.031 *    P<0.001 **   P=0.003 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCH-ARM / FISHERS |     P=0.133      P=0.034 *    P<0.001 **   P=0.040 *   |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Hepatocyte                                                                                                                |
|     Erythrophagocytosis                                                                                                         |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    9/50 (18%)   13/50 (26%)  6/49 (12%)  |1/49 (2%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     2.1%         19.2%        27.5%        15.0%       |2.3%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/45 (2%)    9/41 (22%)   13/43 (30%)  5/23 (22%)  |1/35 (3%)    0/42 (0%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      497         |730 (T)      ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.037 *    P=0.006 **   P<0.001 **   P=0.007 **  |P=0.454N     P=0.464N     P=0.500N     P=0.464N     |
|POLY 3             |     P=0.202      P=0.007 **   P<0.001 **   P=0.032 *   |P=0.477N     P=0.489N     P=0.497N     P=0.496N     |
|POLY 1.5           |     P=0.279      P=0.008 **   P<0.001 **   P=0.041 *   |P=0.476N     P=0.491N     P=0.496N     P=0.499N     |
|POLY 6             |     P=0.116      P=0.006 **   P<0.001 **   P=0.022 *   |P=0.479N     P=0.486N     P=0.501N     P=0.490N     |
|LOGISTIC REGRESSION|     P=0.139      P=0.006 **   P<0.001 **   P=0.044 *   |P=0.454N     (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.373      P=0.008 **   P<0.001 **   P=0.053     |P=0.473N     P=0.495N     P=0.495N     P=0.500N     |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 14
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Congestion                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    2/50 (4%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         4.4%         0.0%         |
|TERMINAL (d)       |     0/45 (0%)    0/41 (0%)    0/43 (0%)    0/23 (0%)   |0/35 (0%)    0/42 (0%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          675          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.680N     (e)          P=0.234      (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.698N     (e)          P=0.239      (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.702N     (e)          P=0.239      (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.690N     (e)          P=0.238      (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.690N     (e)          P=0.229      (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.700N     (e)          P=0.247      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Hemorrhage                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|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%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         4.2%         2.2%         0.0%         |
|TERMINAL (d)       |     0/45 (0%)    0/41 (0%)    0/43 (0%)    0/23 (0%)   |0/35 (0%)    1/42 (2%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          519          505          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.384N     P=0.260      P=0.500      (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.380N     P=0.249      P=0.503      (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.387N     P=0.245      P=0.503      (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.369N     P=0.255      P=0.502      (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.289N     P=0.173      P=0.354      (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.390N     P=0.247      P=0.500      (e)          |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 15
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung: Alveolar Epithelium                                                                                                        |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    1/50 (2%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    2/50 (4%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     2.1%         2.1%         2.1%         0.0%        |0.0%         0.0%         4.4%         0.0%         |
|TERMINAL (d)       |     0/45 (0%)    1/41 (2%)    1/43 (2%)    0/23 (0%)   |0/35 (0%)    0/42 (0%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     710          729 (T)      729 (T)      ---         |---          ---          626          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.467N     P=0.740      P=0.753      P=0.638N    |P=0.685N     (e)          P=0.237      (e)          |
|POLY 3             |     P=0.364N     P=0.754      P=0.757      P=0.537N    |P=0.698N     (e)          P=0.240      (e)          |
|POLY 1.5           |     P=0.346N     P=0.758      P=0.760      P=0.519N    |P=0.702N     (e)          P=0.240      (e)          |
|POLY 6             |     P=0.389N     P=0.749      P=0.755      P=0.563N    |P=0.690N     (e)          P=0.239      (e)          |
|LOGISTIC REGRESSION|     P=0.401N     P=0.760      P=0.762      P=0.545N    |P=0.674N     (e)          P=0.213      (e)          |
|COCH-ARM / FISHERS |     P=0.323N     P=0.753N     P=0.753N     P=0.500N    |P=0.700N     (e)          P=0.247      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery: Fat                                                                                                                   |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/2 (100%)   2/2 (100%)   0/1 (0%)     5/5 (100%)  |4/6 (67%)    3/4 (75%)    2/6 (33%)    7/7 (100%)   |
|POLY-3 ADJUSTED (b)|     100.0%       100.0%       0.0%         100.0%      |66.7%        86.0%        40.3%        100.0%       |
|TERMINAL (d)       |     2/2 (100%)   1/1 (100%)   0/1 (0%)     1/1 (100%)  |1/3 (33%)    3/3 (100%)   2/2 (100%)   4/4 (100%)   |
|FIRST INCIDENCE    |     729 (T)      666          ---          586         |617          730 (T)      730 (T)      477          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.005 **   (e)          P=0.362N     (e)         |P=0.127      P=0.477N     P=0.437N     P=0.352      |
|POLY 3             |     P=1.000N     (e)          P=1.000N     (e)         |P=0.097      P=0.542      P=0.399N     P=0.178      |
|POLY 1.5           |     P=1.000N     (e)          P=1.000N     (e)         |P=0.094      P=0.591      P=0.344N     P=0.178      |
|POLY 6             |     P=1.000N     (e)          P=1.000N     (e)         |P=0.104      P=0.472      P=0.496N     P=0.178      |
|LOGISTIC REGRESSION|     P=0.005 **   (e)          (e)          (e)         |P=0.073      P=0.620      P=0.355N     (e)          |
|COCH-ARM / FISHERS |     P=0.602      (e)          P=0.333N     (e)         |P=0.112      P=0.667      P=0.284N     P=0.192      |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 16
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    1/50 (2%)    2/50 (4%)   |2/50 (4%)    0/50 (0%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     4.2%         6.4%         2.1%         4.9%        |4.5%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     2/45 (4%)    3/41 (7%)    1/43 (2%)    0/23 (0%)   |1/35 (3%)    0/42 (0%)    0/34 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      554         |701          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.494      P=0.458      P=0.516N     P=0.533     |P=0.230N     P=0.212N     P=0.255N     P=0.212N     |
|POLY 3             |     P=0.595N     P=0.488      P=0.505N     P=0.633     |P=0.245N     P=0.229N     P=0.243N     P=0.236N     |
|POLY 1.5           |     P=0.570N     P=0.497      P=0.501N     P=0.663     |P=0.244N     P=0.232N     P=0.241N     P=0.241N     |
|POLY 6             |     P=0.594      P=0.478      P=0.508N     P=0.588     |P=0.246N     P=0.225N     P=0.246N     P=0.229N     |
|LOGISTIC REGRESSION|     P=0.533N     P=0.458      P=0.516N     P=0.673N    |P=0.240N     P=0.229N     P=0.244N     P=0.236N     |
|COCH-ARM / FISHERS |     P=0.541N     P=0.500      P=0.500N     P=0.691N    |P=0.241N     P=0.247N     P=0.253N     P=0.253N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |0/45 (0%)    0/50 (0%)    0/49 (0%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|                                                        |0.0%         0.0%         0.0%         4.4%         |
|TERMINAL (d)       |                                                        |0/33 (0%)    0/42 (0%)    0/34 (0%)    1/42 (2%)    |
|FIRST INCIDENCE    |                                                        |---          ---          ---          549          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.048 *    (e)          (e)          P=0.264      |
|POLY 3             |                                                        |P=0.044 *    (e)          (e)          P=0.266      |
|POLY 1.5           |                                                        |P=0.043 *    (e)          (e)          P=0.260      |
|POLY 6             |                                                        |P=0.046 *    (e)          (e)          P=0.274      |
|LOGISTIC REGRESSION|                                                        |P=0.054      (e)          (e)          P=0.263      |
|COCH-ARM / FISHERS |                                                        |P=0.044 *    (e)          (e)          P=0.269      |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 17
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |3/45 (7%)    4/50 (8%)    7/49 (14%)   5/49 (10%)   |
|POLY-3 ADJUSTED (b)|                                                        |7.4%         8.6%         15.7%        10.9%        |
|TERMINAL (d)       |                                                        |2/33 (6%)    4/42 (10%)   4/34 (12%)   4/42 (10%)   |
|FIRST INCIDENCE    |                                                        |627          730 (T)      627          549          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.443      P=0.614      P=0.171      P=0.461      |
|POLY 3             |                                                        |P=0.401      P=0.574      P=0.196      P=0.422      |
|POLY 1.5           |                                                        |P=0.386      P=0.569      P=0.198      P=0.410      |
|POLY 6             |                                                        |P=0.423      P=0.579      P=0.191      P=0.439      |
|LOGISTIC REGRESSION|                                                        |P=0.384      P=0.577      P=0.195      P=0.404      |
|COCH-ARM / FISHERS |                                                        |P=0.386      P=0.559      P=0.195      P=0.406      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    2/50 (4%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         4.3%         0.0%         0.0%         |
|TERMINAL (d)       |     0/45 (0%)    0/41 (0%)    0/43 (0%)    0/23 (0%)   |0/35 (0%)    1/42 (2%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          648          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.366N     P=0.268      (e)          (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.372N     P=0.248      (e)          (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.378N     P=0.244      (e)          (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.363N     P=0.253      (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.381N     P=0.227      (e)          (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.384N     P=0.247      (e)          (e)          |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 18
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas: Acinus                                                                                                                 |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |2/50 (4%)    1/50 (2%)    2/50 (4%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     4.1%         2.1%         0.0%         2.5%        |4.5%         2.1%         4.4%         2.2%         |
|TERMINAL (d)       |     1/45 (2%)    1/41 (2%)    0/43 (0%)    0/23 (0%)   |2/35 (6%)    0/42 (0%)    1/35 (3%)    1/42 (2%)    |
|FIRST INCIDENCE    |     662          729 (T)      ---          690         |730 (T)      549          631          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.671N     P=0.529N     P=0.247N     P=0.686N    |P=0.446N     P=0.458N     P=0.693      P=0.436N     |
|POLY 3             |     P=0.520N     P=0.511N     P=0.242N     P=0.565N    |P=0.486N     P=0.482N     P=0.691N     P=0.498N     |
|POLY 1.5           |     P=0.513N     P=0.504N     P=0.239N     P=0.533N    |P=0.490N     P=0.488N     P=0.690N     P=0.505N     |
|POLY 6             |     P=0.526N     P=0.520N     P=0.245N     P=0.608N    |P=0.478N     P=0.473N     P=0.694N     P=0.486N     |
|LOGISTIC REGRESSION|     P=0.509N     P=0.500N     P=0.240N     P=0.511N    |P=0.474N     P=0.534N     P=0.694N     P=0.436N     |
|COCH-ARM / FISHERS |     P=0.500N     P=0.500N     P=0.247N     P=0.500N    |P=0.484N     P=0.500N     P=0.691N     P=0.508N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Peripheral Nerve: Axon                                                                                                           |
|     Degeneration                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/0 (0%)     0/0 (0%)     1/1 (100%)   0/0 (0%)    |2/2 (100%)   0/0 (0%)     0/1 (0%)     0/0 (0%)     |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         100.0%       0.0%        |100.0%       0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     ---          ---          727          ---         |554          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.321N     (e)          P=0.242N     (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          (e)          P=1.000      (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          (e)          P=1.000      (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          (e)          P=1.000N     (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.807N     (e)          P=0.333N     (e)          |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 19
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland                                                                                                                  |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/48 (0%)    0/48 (0%)    0/47 (0%)    0/46 (0%)   |2/47 (4%)    0/50 (0%)    1/48 (2%)    0/46 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |4.7%         0.0%         2.3%         0.0%         |
|TERMINAL (d)       |     0/43 (0%)    0/39 (0%)    0/41 (0%)    0/22 (0%)   |2/33 (6%)    0/42 (0%)    0/35 (0%)    0/39 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |730 (T)      ---          675          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.255N     P=0.187N     P=0.486N     P=0.202N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.279N     P=0.216N     P=0.494N     P=0.239N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.280N     P=0.219N     P=0.492N     P=0.243N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.278N     P=0.213N     P=0.496N     P=0.232N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.276N     (e)          P=0.495N     (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.275N     P=0.232N     P=0.492N     P=0.253N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis                                                                                                   |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/48 (2%)    0/48 (0%)    2/47 (4%)    0/46 (0%)   |8/47 (17%)   4/50 (8%)    12/48 (25%)  6/46 (13%)   |
|POLY-3 ADJUSTED (b)|     2.2%         0.0%         4.5%         0.0%        |18.7%        8.6%         27.9%        14.2%        |
|TERMINAL (d)       |     1/43 (2%)    0/39 (0%)    2/41 (5%)    0/22 (0%)   |7/33 (21%)   4/42 (10%)   12/35 (34%)  5/39 (13%)   |
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      ---         |627          730 (T)      730 (T)      681          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.619N     P=0.519N     P=0.483      P=0.634N    |P=0.428N     P=0.089N     P=0.263      P=0.277N     |
|POLY 3             |     P=0.516N     P=0.505N     P=0.488      P=0.543N    |P=0.539N     P=0.137N     P=0.225      P=0.395N     |
|POLY 1.5           |     P=0.491N     P=0.502N     P=0.492      P=0.526N    |P=0.551N     P=0.141N     P=0.236      P=0.407N     |
|POLY 6             |     P=0.551N     P=0.510N     P=0.486      P=0.566N    |P=0.515N     P=0.132N     P=0.208      P=0.374N     |
|LOGISTIC REGRESSION|     P=0.619N     (e)          P=0.483      (e)         |P=0.499N     P=0.129N     P=0.213      P=0.387N     |
|COCH-ARM / FISHERS |     P=0.462N     P=0.500N     P=0.492      P=0.511N    |P=0.535N     P=0.149N     P=0.242      P=0.403N     |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 20
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     22/50 (44%)  25/50 (50%)  32/49 (65%)  22/49 (45%) |                                                    |
|POLY-3 ADJUSTED (b)|     45.8%        51.3%        69.1%        51.7%       |                                                    |
|TERMINAL (d)       |     21/45 (47%)  20/41 (49%)  32/42 (76%)  13/23 (57%) |                                                    |
|FIRST INCIDENCE    |     710          464          729 (T)      497         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.003 **   P=0.222      P=0.010 *    P=0.010 *   |                                                    |
|POLY 3             |     P=0.378      P=0.366      P=0.016 *    P=0.359     |                                                    |
|POLY 1.5           |     P=0.514      P=0.370      P=0.021 *    P=0.456     |                                                    |
|POLY 6             |     P=0.213      P=0.363      P=0.013 *    P=0.236     |                                                    |
|LOGISTIC REGRESSION|     P=0.355      P=0.339      P=0.013 *    P=0.320     |                                                    |
|COCH-ARM / FISHERS |     P=0.444N     P=0.344      P=0.027 *    P=0.545     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/50 (14%)   4/50 (8%)    4/49 (8%)    4/49 (8%)   |                                                    |
|POLY-3 ADJUSTED (b)|     14.3%        8.5%         8.6%         10.2%       |                                                    |
|TERMINAL (d)       |     5/45 (11%)   3/41 (7%)    3/42 (7%)    4/23 (17%)  |                                                    |
|FIRST INCIDENCE    |     550          662          711          729 (T)     |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.474      P=0.314N     P=0.299N     P=0.608     |                                                    |
|POLY 3             |     P=0.439N     P=0.284N     P=0.292N     P=0.401N    |                                                    |
|POLY 1.5           |     P=0.391N     P=0.270N     P=0.281N     P=0.337N    |                                                    |
|POLY 6             |     P=0.504N     P=0.300N     P=0.302N     P=0.495N    |                                                    |
|LOGISTIC REGRESSION|     P=0.412N     P=0.263N     P=0.274N     P=0.356N    |                                                    |
|COCH-ARM / FISHERS |     P=0.333N     P=0.262N     P=0.274N     P=0.274N    |                                                    |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 21
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Inflammation Granulomatous                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    4/50 (8%)    0/49 (0%)    1/49 (2%)   |                                                    |
|POLY-3 ADJUSTED (b)|     0.0%         8.6%         0.0%         2.6%        |                                                    |
|TERMINAL (d)       |     0/45 (0%)    4/41 (10%)   0/42 (0%)    1/23 (4%)   |                                                    |
|FIRST INCIDENCE    |     ---          729 (T)      ---          729 (T)     |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.641      P=0.052      (e)          P=0.366     |                                                    |
|POLY 3             |     P=0.546N     P=0.057      (e)          P=0.460     |                                                    |
|POLY 1.5           |     P=0.521N     P=0.060      (e)          P=0.477     |                                                    |
|POLY 6             |     P=0.576N     P=0.054      (e)          P=0.435     |                                                    |
|LOGISTIC REGRESSION|     (e)          P=0.052      (e)          P=0.366     |                                                    |
|COCH-ARM / FISHERS |     P=0.494N     P=0.059      (e)          P=0.495     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Seminal Vesicle                                                                                                                  |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/50 (14%)   3/50 (6%)    4/50 (8%)    0/50 (0%)   |                                                    |
|POLY-3 ADJUSTED (b)|     14.6%        6.4%         8.5%         0.0%        |                                                    |
|TERMINAL (d)       |     7/45 (16%)   3/41 (7%)    4/43 (9%)    0/23 (0%)   |                                                    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      ---         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.059N     P=0.198N     P=0.287N     P=0.059N    |                                                    |
|POLY 3             |     P=0.025N*    P=0.169N     P=0.270N     P=0.016N*   |                                                    |
|POLY 1.5           |     P=0.019N*    P=0.161N     P=0.263N     P=0.011N*   |                                                    |
|POLY 6             |     P=0.035N*    P=0.178N     P=0.275N     P=0.026N*   |                                                    |
|LOGISTIC REGRESSION|     P=0.059N     P=0.198N     P=0.287N     (e)         |                                                    |
|COCH-ARM / FISHERS |     P=0.015N*    P=0.159N     P=0.262N     P=0.006N**  |                                                    |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 22
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hematopoietic Cell Proliferation                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     12/50 (24%)  14/50 (28%)  12/49 (24%)  30/42 (71%) |9/45 (20%)   17/49 (35%)  17/48 (35%)  26/48 (54%)  |
|POLY-3 ADJUSTED (b)|     24.7%        29.0%        24.6%        74.3%       |21.0%        36.0%        36.8%        56.2%        |
|TERMINAL (d)       |     10/45 (22%)  9/41 (22%)   8/43 (19%)   15/23 (65%) |4/35 (11%)   14/42 (33%)  9/35 (26%)   22/42 (52%)  |
|FIRST INCIDENCE    |     550          464          453          456         |554          519          491          186          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.327      P=0.547      P<0.001 **  |P=0.005 **   P=0.133      P=0.072      P=0.004 **   |
|POLY 3             |     P<0.001 **   P=0.401      P=0.591N     P<0.001 **  |P<0.001 **   P=0.091      P=0.079      P<0.001 **   |
|POLY 1.5           |     P<0.001 **   P=0.413      P=0.591N     P<0.001 **  |P<0.001 **   P=0.091      P=0.080      P<0.001 **   |
|POLY 6             |     P<0.001 **   P=0.388      P=0.589N     P<0.001 **  |P<0.001 **   P=0.090      P=0.076      P<0.001 **   |
|LOGISTIC REGRESSION|     P<0.001 **   P=0.408      P=0.551      P<0.001 **  |P<0.001 **   P=0.078      P=0.071      P<0.001 **   |
|COCH-ARM / FISHERS |     P<0.001 **   P=0.410      P=0.570      P<0.001 **  |P<0.001 **   P=0.086      P=0.077      P<0.001 **   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen: Lymphoid Follicle                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    0/50 (0%)    1/49 (2%)    0/42 (0%)   |8/45 (18%)   4/49 (8%)    5/48 (10%)   6/48 (13%)   |
|POLY-3 ADJUSTED (b)|     8.3%         0.0%         2.1%         0.0%        |19.3%        8.7%         11.4%        13.6%        |
|TERMINAL (d)       |     4/45 (9%)    0/41 (0%)    1/43 (2%)    0/23 (0%)   |8/35 (23%)   4/42 (10%)   4/35 (11%)   6/42 (14%)   |
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      ---         |730 (T)      730 (T)      675          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.166N     P=0.076N     P=0.194N     P=0.178N    |P=0.442N     P=0.100N     P=0.274N     P=0.251N     |
|POLY 3             |     P=0.117N     P=0.064N     P=0.185N     P=0.108N    |P=0.515N     P=0.130N     P=0.235N     P=0.335N     |
|POLY 1.5           |     P=0.114N     P=0.062N     P=0.183N     P=0.096N    |P=0.521N     P=0.132N     P=0.232N     P=0.343N     |
|POLY 6             |     P=0.121N     P=0.067N     P=0.187N     P=0.128N    |P=0.503N     P=0.127N     P=0.242N     P=0.321N     |
|LOGISTIC REGRESSION|     P=0.166N     (e)          P=0.194N     (e)         |P=0.480N     P=0.100N     P=0.262N     P=0.251N     |
|COCH-ARM / FISHERS |     P=0.111N     P=0.059N     P=0.187N     P=0.082N    |P=0.509N     P=0.139N     P=0.235N     P=0.337N     |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 23
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Ulcer                                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/49 (2%)    0/50 (0%)    2/50 (4%)   |4/50 (8%)    1/50 (2%)    1/50 (2%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.2%         0.0%         4.9%        |8.7%         2.1%         2.2%         4.3%         |
|TERMINAL (d)       |     0/45 (0%)    0/40 (0%)    0/43 (0%)    0/23 (0%)   |2/35 (6%)    0/42 (0%)    0/35 (0%)    1/42 (2%)    |
|FIRST INCIDENCE    |     ---          666          ---          570         |554          549          631          186          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.094      P=0.487      (e)          P=0.191     |P=0.443N     P=0.164N     P=0.184N     P=0.305N     |
|POLY 3             |     P=0.127      P=0.492      (e)          P=0.202     |P=0.468N     P=0.170N     P=0.184N     P=0.335N     |
|POLY 1.5           |     P=0.137      P=0.495      (e)          P=0.219     |P=0.470N     P=0.173N     P=0.180N     P=0.342N     |
|POLY 6             |     P=0.114      P=0.488      (e)          P=0.181     |P=0.463N     P=0.167N     P=0.189N     P=0.325N     |
|LOGISTIC REGRESSION|     P=0.171      P=0.485      (e)          P=0.241     |P=0.308N     P=0.244N     P=0.206N     P=0.285N     |
|COCH-ARM / FISHERS |     P=0.150      P=0.495      (e)          P=0.247     |P=0.468N     P=0.181N     P=0.181N     P=0.349N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach: Epithelium                                                                                                 |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/49 (0%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    1/50 (2%)    1/50 (2%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         5.0%        |0.0%         2.1%         2.2%         2.2%         |
|TERMINAL (d)       |     0/45 (0%)    0/40 (0%)    0/43 (0%)    2/23 (9%)   |0/35 (0%)    1/42 (2%)    1/35 (3%)    1/42 (2%)    |
|FIRST INCIDENCE    |     ---          ---          ---          729 (T)     |---          730 (T)      730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.009 **   (e)          (e)          P=0.107     |P=0.515      P=0.536      P=0.500      P=0.536      |
|POLY 3             |     P=0.034 *    (e)          (e)          P=0.198     |P=0.485      P=0.508      P=0.500      P=0.501      |
|POLY 1.5           |     P=0.037 *    (e)          (e)          P=0.217     |P=0.478      P=0.505      P=0.501      P=0.497      |
|POLY 6             |     P=0.030 *    (e)          (e)          P=0.175     |P=0.497      P=0.512      P=0.497      P=0.508      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.107     |(e)          P=0.536      P=0.500      P=0.536      |
|COCH-ARM / FISHERS |     P=0.042 *    (e)          (e)          P=0.247     |P=0.478      P=0.500      P=0.500      P=0.495      |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 24
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Ulcer                                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |1/50 (2%)    0/50 (0%)    1/50 (2%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     4.2%         0.0%         0.0%         2.5%        |2.2%         0.0%         2.2%         0.0%         |
|TERMINAL (d)       |     1/45 (2%)    0/41 (0%)    0/43 (0%)    0/23 (0%)   |0/35 (0%)    0/42 (0%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     710          ---          ---          569         |554          ---          676          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.649      P=0.260N     P=0.247N     P=0.663N    |P=0.459N     P=0.504N     P=0.755      P=0.508N     |
|POLY 3             |     P=0.652N     P=0.244N     P=0.241N     P=0.561N    |P=0.466N     P=0.494N     P=0.759      P=0.501N     |
|POLY 1.5           |     P=0.651N     P=0.239N     P=0.238N     P=0.531N    |P=0.468N     P=0.496N     P=0.760N     P=0.504N     |
|POLY 6             |     P=0.648N     P=0.249N     P=0.243N     P=0.602N    |P=0.463N     P=0.492N     P=0.756      P=0.496N     |
|LOGISTIC REGRESSION|     P=0.619N     P=0.240N     P=0.238N     P=0.481N    |P=0.404N     P=0.616N     P=0.726      P=0.464N     |
|COCH-ARM / FISHERS |     P=0.646N     P=0.247N     P=0.247N     P=0.500N    |P=0.464N     P=0.500N     P=0.753N     P=0.505N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular: Epithelium                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    2/50 (4%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         4.3%         0.0%         0.0%         |
|TERMINAL (d)       |     0/45 (0%)    0/41 (0%)    0/43 (0%)    0/23 (0%)   |0/35 (0%)    2/42 (5%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          730 (T)      ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.359N     P=0.279      (e)          (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.373N     P=0.246      (e)          (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.378N     P=0.243      (e)          (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.364N     P=0.251      (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          P=0.279      (e)          (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.384N     P=0.247      (e)          (e)          |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 25
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes: Germinal Epithelium                                                                                                      |
|     Degeneration                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/49 (0%)    2/50 (4%)    3/50 (6%)   |                                                    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         4.2%         7.4%        |                                                    |
|TERMINAL (d)       |     0/45 (0%)    0/40 (0%)    1/43 (2%)    1/23 (4%)   |                                                    |
|FIRST INCIDENCE    |     ---          ---          727          569         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.007 **   (e)          P=0.232      P=0.054     |                                                    |
|POLY 3             |     P=0.024 *    (e)          P=0.234      P=0.091     |                                                    |
|POLY 1.5           |     P=0.030 *    (e)          P=0.237      P=0.104     |                                                    |
|POLY 6             |     P=0.018 *    (e)          P=0.232      P=0.076     |                                                    |
|LOGISTIC REGRESSION|     P=0.040 *    (e)          P=0.232      P=0.129     |                                                    |
|COCH-ARM / FISHERS |     P=0.038 *    (e)          P=0.247      P=0.121     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes: Germinal Epithelium                                                                                                      |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/49 (0%)    1/50 (2%)    1/50 (2%)   |                                                    |
|POLY-3 ADJUSTED (b)|     4.2%         0.0%         2.1%         2.5%        |                                                    |
|TERMINAL (d)       |     2/45 (4%)    0/40 (0%)    1/43 (2%)    0/23 (0%)   |                                                    |
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      664         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.577      P=0.265N     P=0.516N     P=0.701N    |                                                    |
|POLY 3             |     P=0.642N     P=0.248N     P=0.505N     P=0.562N    |                                                    |
|POLY 1.5           |     P=0.629N     P=0.244N     P=0.501N     P=0.532N    |                                                    |
|POLY 6             |     P=0.644      P=0.253N     P=0.508N     P=0.604N    |                                                    |
|LOGISTIC REGRESSION|     P=0.668N     (e)          P=0.516N     P=0.564N    |                                                    |
|COCH-ARM / FISHERS |     P=0.611N     P=0.253N     P=0.500N     P=0.500N    |                                                    |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 26
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicle                                                                                                          |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/49 (0%)    0/46 (0%)   |2/45 (4%)    1/48 (2%)    0/48 (0%)    0/48 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |4.8%         2.2%         0.0%         0.0%         |
|TERMINAL (d)       |     0/45 (0%)    0/41 (0%)    0/43 (0%)    0/23 (0%)   |1/35 (3%)    0/42 (0%)    0/35 (0%)    0/42 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |627          549          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.166N     P=0.474N     P=0.240N     P=0.215N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.165N     P=0.468N     P=0.227N     P=0.225N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.165N     P=0.470N     P=0.224N     P=0.226N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.164N     P=0.465N     P=0.232N     P=0.222N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.127N     P=0.552N     P=0.229N     P=0.218N     |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.163N     P=0.476N     P=0.231N     P=0.231N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/50 (14%)   10/50 (20%)  15/49 (31%)  21/46 (46%) |10/45 (22%)  14/48 (29%)  16/48 (33%)  15/48 (31%)  |
|POLY-3 ADJUSTED (b)|     14.6%        21.3%        32.3%        55.1%       |23.8%        30.9%        36.2%        34.0%        |
|TERMINAL (d)       |     7/45 (16%)   9/41 (22%)   15/43 (35%)  20/23 (87%) |9/35 (26%)   14/42 (33%)  15/35 (43%)  15/42 (36%)  |
|FIRST INCIDENCE    |     729 (T)      657          729 (T)      638         |554          730 (T)      626          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.232      P=0.033 *    P<0.001 **  |P=0.377      P=0.412      P=0.119      P=0.331      |
|POLY 3             |     P<0.001 **   P=0.281      P=0.035 *    P<0.001 **  |P=0.259      P=0.308      P=0.152      P=0.212      |
|POLY 1.5           |     P<0.001 **   P=0.294      P=0.038 *    P<0.001 **  |P=0.256      P=0.308      P=0.163      P=0.211      |
|POLY 6             |     P<0.001 **   P=0.267      P=0.033 *    P<0.001 **  |P=0.271      P=0.310      P=0.136      P=0.220      |
|LOGISTIC REGRESSION|     P<0.001 **   P=0.258      P=0.033 *    P<0.001 **  |P=0.291      P=0.326      P=0.152      P=0.230      |
|COCH-ARM / FISHERS |     P<0.001 **   P=0.298      P=0.040 *    P<0.001 **  |P=0.285      P=0.299      P=0.168      P=0.228      |
|=================================================================================================================================|
       Date:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 27
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Tooth                                                                                                                            |
|     Malformation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     14/14 (100%) 19/19 (100%) 14/14 (100%) 5/5 (100%)  |0/1 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|POLY-3 ADJUSTED (b)|     100.0%       100.0%       100.0%       100.0%      |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     14/14 (100%) 17/17 (100%) 13/13 (100%) 4/4 (100%)  |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     729 (T)      658          711          638         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder: Transitional Epithelium                                                                                         |
|     Inclusion Body Intracytoplasmic                                                                                             |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    46/49 (94%)  46/49 (94%)  42/45 (93%) |0/44 (0%)    40/48 (83%)  43/46 (93%)  46/48 (96%)  |
|POLY-3 ADJUSTED (b)|     0.0%         94.9%        93.9%        96.3%       |0.0%         84.5%        93.7%        97.8%        |
|TERMINAL (d)       |     0/45 (0%)    40/41 (98%)  41/43 (95%)  23/23 (100%)|0/35 (0%)    35/42 (83%)  33/35 (94%)  41/42 (98%)  |
|FIRST INCIDENCE    |     ---          456          453          490         |---          519          491          186          |
|-------------------|                                                        |                                                    |
|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:  05/27/99                           EXPERIMENT: 88036 TEST: 04                                            Page 28
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                   ANTHRAQUINONE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |2/50 (4%)    0/50 (0%)    1/50 (2%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|                                                        |4.5%         0.0%         2.2%         2.2%         |
|TERMINAL (d)       |                                                        |2/35 (6%)    0/42 (0%)    1/35 (3%)    1/42 (2%)    |
|FIRST INCIDENCE    |                                                        |730 (T)      ---          730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.576N     P=0.199N     P=0.500N     P=0.436N     |
|POLY 3             |                                                        |P=0.624N     P=0.228N     P=0.500N     P=0.498N     |
|POLY 1.5           |                                                        |P=0.625N     P=0.231N     P=0.498N     P=0.505N     |
|POLY 6             |                                                        |P=0.620N     P=0.224N     P=0.504N     P=0.486N     |
|LOGISTIC REGRESSION|                                                        |P=0.576N     (e)          P=0.500N     P=0.436N     |
|COCH-ARM / FISHERS |                                                        |P=0.621N     P=0.247N     P=0.500N     P=0.508N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 PPM        833 PPM      2500 PPM     7500 PPM    |0 PPM        833 PPM      2500 PPM     7500 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus: Endometrium                                                                                                              |
|     Hyperplasia Cystic                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |35/50 (70%)  38/50 (76%)  23/50 (46%)  39/49 (80%)  |
|POLY-3 ADJUSTED (b)|                                                        |76.1%        79.4%        50.9%        85.4%        |
|TERMINAL (d)       |                                                        |32/35 (91%)  35/42 (83%)  21/35 (60%)  37/42 (88%)  |
|FIRST INCIDENCE    |                                                        |554          549          675          625          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.539N     P=0.284N     P=0.005N**   P=0.350N     |
|POLY 3             |                                                        |P=0.146      P=0.445      P=0.007N**   P=0.181      |
|POLY 1.5           |                                                        |P=0.136      P=0.399      P=0.008N**   P=0.156      |
|POLY 6             |                                                        |P=0.186      P=0.519      P=0.007N**   P=0.255      |
|LOGISTIC REGRESSION|                                                        |P=0.246      P=0.452      P=0.009N**   P=0.280      |
|COCH-ARM / FISHERS |                                                        |P=0.190      P=0.326      P=0.013N*    P=0.193      |
|=================================================================================================================================|

(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).