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).