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TDMS Study 56348-03 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10   
LAB: Battelle Columbus                                           CITRAL                                        DATE: 06/01/00     
EXPERIMENT: 56348 TEST: 03                                                                                     TIME: 16:41:21     
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                      
CONT: N01-ES-55384                              ROUTE: DOSED FEED                                              NTP C#: C56348     
PATHOLOGIST: SINGER, ALLEN                                                                                     CAS: 5392-40-5     
 
 

SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF                      CITRAL
===============================================================
 
Male Rats
------------
Organ                                 Morphology
-----                                 ----------
Heart                                  Cardiomyopathy
                                       Thrombosis
Liver                                  Angiectasis
Pituitary Gland: Pars Distalis         Hyperplasia
Prostate                               Inflammation Chronic
Skin                                   Hyperkeratosis
Stomach, Forestomach: Epithelium       Hyperplasia
Thyroid Gland: C-Cell                  Hyperplasia
===============================================================
Female Rats
------------
Organ                                  Morphology
-----                                  ----------
Adrenal Cortex                         Hypertrophy
Clitoral Gland                         Hyperplasia
                                       Inflammation
Heart                                  Cardiomyopathy
Liver                                  Basophilic Focus
Liver: Bile Duct                       Hyperplasia
Lymph Node, Mandibular                 Ectasia
                                       Hyperplasia
Ovary                                  Cyst
Stomach, Forestomach: Epithelium       Hyperplasia
===============================================================

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 1
                     Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hematopoietic Cell Proliferation                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                2/50 (4%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     4.7%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      639          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.225      |                                    (e)             |
|POLY 3             |                                           P=0.234      |                                    (e)             |
|POLY 1.5           |                                           P=0.235      |                                    (e)             |
|POLY 6             |                                           P=0.231      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.253      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.247      |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  12/50 (24%)              13/50 (26%)  |           14/50 (28%)              16/50 (32%)     |
|POLY-3 ADJUSTED (b)|                  26.9%                    30.0%        |           30.6%                    33.8%           |
|TERMINAL (d)       |                  8/30 (27%)               6/22 (27%)   |           12/35 (34%)              14/40 (35%)     |
|FIRST INCIDENCE    |                  600                      617          |           627                      677             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.288      |                                    P=0.584         |
|POLY 3             |                                           P=0.469      |                                    P=0.457         |
|POLY 1.5           |                                           P=0.481      |                                    P=0.428         |
|POLY 6             |                                           P=0.452      |                                    P=0.496         |
|LOGISTIC REGRESSION|                                           P=0.460      |                                    P=0.514         |
|COCH-ARM / FISHERS |                                           P=0.500      |                                    P=0.414         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 2
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hypertrophy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                0/50 (0%)    |           10/50 (20%)              4/50 (8%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     0.0%         |           21.9%                    8.5%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           9/35 (26%)               4/40 (10%)      |
|FIRST INCIDENCE    |                  ---                      ---          |           627                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           (e)          |                                    P=0.043N*       |
|POLY 3             |                                           (e)          |                                    P=0.062N        |
|POLY 1.5           |                                           (e)          |                                    P=0.069N        |
|POLY 6             |                                           (e)          |                                    P=0.054N        |
|LOGISTIC REGRESSION|                                           (e)          |                                    P=0.053N        |
|COCH-ARM / FISHERS |                                           (e)          |                                    P=0.074N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  3/50 (6%)                1/50 (2%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  6.8%                     2.4%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  549                      660          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.358N     |                                    (e)             |
|POLY 3             |                                           P=0.330N     |                                    (e)             |
|POLY 1.5           |                                           P=0.320N     |                                    (e)             |
|POLY 6             |                                           P=0.347N     |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.278N     |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.309N     |                                    (e)             |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 3
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Vacuolization Cytoplasmic                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  4/50 (8%)                7/50 (14%)   |           1/50 (2%)                2/50 (4%)       |
|POLY-3 ADJUSTED (b)|                  9.1%                     16.3%        |           2.2%                     4.2%            |
|TERMINAL (d)       |                  1/30 (3%)                4/22 (18%)   |           0/35 (0%)                2/40 (5%)       |
|FIRST INCIDENCE    |                  660                      509          |           622                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.179      |                                    P=0.538         |
|POLY 3             |                                           P=0.245      |                                    P=0.508         |
|POLY 1.5           |                                           P=0.253      |                                    P=0.502         |
|POLY 6             |                                           P=0.232      |                                    P=0.515         |
|LOGISTIC REGRESSION|                                           P=0.264      |                                    P=0.500         |
|COCH-ARM / FISHERS |                                           P=0.262      |                                    P=0.500         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  12/50 (24%)              16/50 (32%)  |           8/49 (16%)               3/50 (6%)       |
|POLY-3 ADJUSTED (b)|                  27.3%                    36.9%        |           17.9%                    6.3%            |
|TERMINAL (d)       |                  9/30 (30%)               7/22 (32%)   |           5/34 (15%)               1/40 (3%)       |
|FIRST INCIDENCE    |                  674                      623          |           627                      697             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.101      |                                    P=0.073N        |
|POLY 3             |                                           P=0.229      |                                    P=0.081N        |
|POLY 1.5           |                                           P=0.237      |                                    P=0.088N        |
|POLY 6             |                                           P=0.221      |                                    P=0.072N        |
|LOGISTIC REGRESSION|                                           P=0.185      |                                    P=0.091N        |
|COCH-ARM / FISHERS |                                           P=0.252      |                                    P=0.094N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 4
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Osteopetrosis                                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                0/50 (0%)    |           3/50 (6%)                3/50 (6%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     0.0%         |           6.6%                     6.3%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           3/35 (9%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  ---                      ---          |           732 (T)                  687             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           (e)          |                                    P=0.597N        |
|POLY 3             |                                           (e)          |                                    P=0.637N        |
|POLY 1.5           |                                           (e)          |                                    P=0.652N        |
|POLY 6             |                                           (e)          |                                    P=0.615N        |
|LOGISTIC REGRESSION|                                           (e)          |                                    P=0.648N        |
|COCH-ARM / FISHERS |                                           (e)          |                                    P=0.661N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  14/50 (28%)              16/50 (32%)  |           11/50 (22%)              9/50 (18%)      |
|POLY-3 ADJUSTED (b)|                  31.1%                    36.0%        |           23.5%                    18.6%           |
|TERMINAL (d)       |                  10/30 (33%)              9/22 (41%)   |           5/35 (14%)               5/40 (13%)      |
|FIRST INCIDENCE    |                  610                      365          |           588                      62              |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.198      |                                    P=0.333N        |
|POLY 3             |                                           P=0.396      |                                    P=0.366N        |
|POLY 1.5           |                                           P=0.406      |                                    P=0.381N        |
|POLY 6             |                                           P=0.371      |                                    P=0.347N        |
|LOGISTIC REGRESSION|                                           P=0.416      |                                    P=0.409N        |
|COCH-ARM / FISHERS |                                           P=0.414      |                                    P=0.402N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 5
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Myelofibrosis                                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                2/50 (4%)    |           1/50 (2%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  4.5%                     4.8%         |           2.2%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  589                      660          |           636                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.672      |                                    P=0.473N        |
|POLY 3             |                                           P=0.681      |                                    P=0.487N        |
|POLY 1.5           |                                           P=0.686      |                                    P=0.496N        |
|POLY 6             |                                           P=0.673      |                                    P=0.476N        |
|LOGISTIC REGRESSION|                                           P=0.663N     |                                    P=0.477N        |
|COCH-ARM / FISHERS |                                           P=0.691N     |                                    P=0.500N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Hemorrhage                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  5/50 (10%)               9/50 (18%)   |           3/50 (6%)                2/50 (4%)       |
|POLY-3 ADJUSTED (b)|                  11.3%                    20.4%        |           6.5%                     4.2%            |
|TERMINAL (d)       |                  0/30 (0%)                1/22 (5%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  674                      610          |           508                      677             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.160      |                                    P=0.454N        |
|POLY 3             |                                           P=0.188      |                                    P=0.491N        |
|POLY 1.5           |                                           P=0.190      |                                    P=0.500N        |
|POLY 6             |                                           P=0.187      |                                    P=0.479N        |
|LOGISTIC REGRESSION|                                           P=0.214      |                                    P=0.461N        |
|COCH-ARM / FISHERS |                                           P=0.194      |                                    P=0.500N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 6
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral Gland                                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |           7/49 (14%)               17/49 (35%)     |
|POLY-3 ADJUSTED (b)|                                                        |           15.7%                    36.6%           |
|TERMINAL (d)       |                                                        |           7/35 (20%)               14/40 (35%)     |
|FIRST INCIDENCE    |                                                        |           732 (T)                  694             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |                                    P=0.040 *       |
|POLY 3             |                                                        |                                    P=0.019 *       |
|POLY 1.5           |                                                        |                                    P=0.016 *       |
|POLY 6             |                                                        |                                    P=0.024 *       |
|LOGISTIC REGRESSION|                                                        |                                    P=0.029 *       |
|COCH-ARM / FISHERS |                                                        |                                    P=0.017 *       |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral Gland                                                                                                                   |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |           13/49 (27%)              22/49 (45%)     |
|POLY-3 ADJUSTED (b)|                                                        |           28.6%                    46.8%           |
|TERMINAL (d)       |                                                        |           9/35 (26%)               20/40 (50%)     |
|FIRST INCIDENCE    |                                                        |           595                      491             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |                                    P=0.114         |
|POLY 3             |                                                        |                                    P=0.052         |
|POLY 1.5           |                                                        |                                    P=0.046 *       |
|POLY 6             |                                                        |                                    P=0.061         |
|LOGISTIC REGRESSION|                                                        |                                    P=0.049 *       |
|COCH-ARM / FISHERS |                                                        |                                    P=0.046 *       |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 7
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral Gland: Duct                                                                                                             |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |           5/49 (10%)               5/49 (10%)      |
|POLY-3 ADJUSTED (b)|                                                        |           11.2%                    10.8%           |
|TERMINAL (d)       |                                                        |           4/35 (11%)               4/40 (10%)      |
|FIRST INCIDENCE    |                                                        |           719                      687             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |                                    P=0.549N        |
|POLY 3             |                                                        |                                    P=0.603N        |
|POLY 1.5           |                                                        |                                    P=0.621N        |
|POLY 6             |                                                        |                                    P=0.580N        |
|LOGISTIC REGRESSION|                                                        |                                    P=0.581N        |
|COCH-ARM / FISHERS |                                                        |                                    P=0.630N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Eye                                                                                                                              |
|     Cataract                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/1 (100%)               3/3 (100%)   |           2/2 (100%)               2/3 (67%)       |
|POLY-3 ADJUSTED (b)|                  100.0%                   100.0%       |           100.0%                   68.9%           |
|TERMINAL (d)       |                  0/0 (0%)                 0/0 (0%)     |           2/2 (100%)               1/1 (100%)      |
|FIRST INCIDENCE    |                  505                      674          |           732 (T)                  687             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           (e)          |                                    P=0.524         |
|POLY 3             |                                           (e)          |                                    P=0.530N        |
|POLY 1.5           |                                           (e)          |                                    P=0.515N        |
|POLY 6             |                                           (e)          |                                    P=0.564N        |
|LOGISTIC REGRESSION|                                           (e)          |                                    P=0.821N        |
|COCH-ARM / FISHERS |                                           (e)          |                                    P=0.600N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 8
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Eye: Retina                                                                                                                      |
|     Degeneration                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/1 (100%)               3/3 (100%)   |           2/2 (100%)               2/3 (67%)       |
|POLY-3 ADJUSTED (b)|                  100.0%                   100.0%       |           100.0%                   68.9%           |
|TERMINAL (d)       |                  0/0 (0%)                 0/0 (0%)     |           2/2 (100%)               1/1 (100%)      |
|FIRST INCIDENCE    |                  505                      674          |           732 (T)                  687             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           (e)          |                                    P=0.524         |
|POLY 3             |                                           (e)          |                                    P=0.530N        |
|POLY 1.5           |                                           (e)          |                                    P=0.515N        |
|POLY 6             |                                           (e)          |                                    P=0.564N        |
|LOGISTIC REGRESSION|                                           (e)          |                                    P=0.821N        |
|COCH-ARM / FISHERS |                                           (e)          |                                    P=0.600N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart                                                                                                                            |
|     Cardiomyopathy                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  39/50 (78%)              43/50 (86%)  |           41/50 (82%)              48/50 (96%)     |
|POLY-3 ADJUSTED (b)|                  81.1%                    90.0%        |           86.5%                    98.0%           |
|TERMINAL (d)       |                  26/30 (87%)              22/22 (100%) |           32/35 (91%)              39/40 (98%)     |
|FIRST INCIDENCE    |                  450                      365          |           508                      491             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.029 *    |                                    P=0.456         |
|POLY 3             |                                           P=0.151      |                                    P=0.026 *       |
|POLY 1.5           |                                           P=0.180      |                                    P=0.016 *       |
|POLY 6             |                                           P=0.111      |                                    P=0.064         |
|LOGISTIC REGRESSION|                                           P=0.181      |                                    P=0.028 *       |
|COCH-ARM / FISHERS |                                           P=0.218      |                                    P=0.026 *       |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 9
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart                                                                                                                            |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                2/50 (4%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     4.7%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      365          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.245      |                                    (e)             |
|POLY 3             |                                           P=0.235      |                                    (e)             |
|POLY 1.5           |                                           P=0.236      |                                    (e)             |
|POLY 6             |                                           P=0.233      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.373      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.247      |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart                                                                                                                            |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                6/50 (12%)   |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     13.8%        |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      365          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.016 *    |                                    (e)             |
|POLY 3             |                                           P=0.015 *    |                                    (e)             |
|POLY 1.5           |                                           P=0.015 *    |                                    (e)             |
|POLY 6             |                                           P=0.015 *    |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.024 *    |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.013 *    |                                    (e)             |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 10
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large, Cecum                                                                                                           |
|     Ulcer                                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/50 (2%)                2/50 (4%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  2.3%                     4.7%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  1/30 (3%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  726 (T)                  446          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.447      |                                    (e)             |
|POLY 3             |                                           P=0.495      |                                    (e)             |
|POLY 1.5           |                                           P=0.497      |                                    (e)             |
|POLY 6             |                                           P=0.491      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.557      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.500      |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large, Colon                                                                                                           |
|     Parasite Metazoan                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  4/50 (8%)                0/50 (0%)    |           2/50 (4%)                2/50 (4%)       |
|POLY-3 ADJUSTED (b)|                  9.2%                     0.0%         |           4.4%                     4.2%            |
|TERMINAL (d)       |                  3/30 (10%)               0/22 (0%)    |           2/35 (6%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  660                      ---          |           732 (T)                  694             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.099N     |                                    P=0.644N        |
|POLY 3             |                                           P=0.068N     |                                    P=0.674N        |
|POLY 1.5           |                                           P=0.065N     |                                    P=0.686N        |
|POLY 6             |                                           P=0.074N     |                                    P=0.657N        |
|LOGISTIC REGRESSION|                                           P=0.073N     |                                    P=0.674N        |
|COCH-ARM / FISHERS |                                           P=0.059N     |                                    P=0.691N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 11
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large, Rectum                                                                                                          |
|     Parasite Metazoan                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  7/50 (14%)               3/50 (6%)    |           7/50 (14%)               4/50 (8%)       |
|POLY-3 ADJUSTED (b)|                  16.0%                    7.2%         |           15.3%                    8.5%            |
|TERMINAL (d)       |                  6/30 (20%)               3/22 (14%)   |           6/35 (17%)               3/40 (8%)       |
|FIRST INCIDENCE    |                  660                      726 (T)      |           588                      708             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.292N     |                                    P=0.201N        |
|POLY 3             |                                           P=0.178N     |                                    P=0.241N        |
|POLY 1.5           |                                           P=0.169N     |                                    P=0.255N        |
|POLY 6             |                                           P=0.194N     |                                    P=0.223N        |
|LOGISTIC REGRESSION|                                           P=0.227N     |                                    P=0.246N        |
|COCH-ARM / FISHERS |                                           P=0.159N     |                                    P=0.262N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small, Ileum                                                                                                           |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                2/50 (4%)    |           0/50 (0%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     4.7%         |           0.0%                     2.1%            |
|TERMINAL (d)       |                  0/30 (0%)                1/22 (5%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  ---                      509          |           ---                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.206      |                                    P=0.527         |
|POLY 3             |                                           P=0.234      |                                    P=0.500         |
|POLY 1.5           |                                           P=0.235      |                                    P=0.500         |
|POLY 6             |                                           P=0.231      |                                    P=0.501         |
|LOGISTIC REGRESSION|                                           P=0.272      |                                    P=0.527         |
|COCH-ARM / FISHERS |                                           P=0.247      |                                    P=0.500         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 12
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small, Jejunum                                                                                                         |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/50 (2%)                3/50 (6%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  2.3%                     7.2%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  1/30 (3%)                3/22 (14%)   |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  726 (T)                  726 (T)      |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.200      |                                    (e)             |
|POLY 3             |                                           P=0.293      |                                    (e)             |
|POLY 1.5           |                                           P=0.299      |                                    (e)             |
|POLY 6             |                                           P=0.285      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.200      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.309      |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Accumulation, Hyaline Droplet                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                2/50 (4%)    |           0/50 (0%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     4.7%         |           0.0%                     2.1%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      365          |           ---                      697             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.225      |                                    P=0.524         |
|POLY 3             |                                           P=0.235      |                                    P=0.500         |
|POLY 1.5           |                                           P=0.236      |                                    P=0.500         |
|POLY 6             |                                           P=0.232      |                                    P=0.501         |
|LOGISTIC REGRESSION|                                           P=0.337      |                                    P=0.500         |
|COCH-ARM / FISHERS |                                           P=0.247      |                                    P=0.500         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 13
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Infarct                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                3/50 (6%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     7.1%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      610          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.116      |                                    (e)             |
|POLY 3             |                                           P=0.116      |                                    (e)             |
|POLY 1.5           |                                           P=0.117      |                                    (e)             |
|POLY 6             |                                           P=0.114      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.134      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.121      |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  45/50 (90%)              42/50 (84%)  |           41/50 (82%)              43/50 (86%)     |
|POLY-3 ADJUSTED (b)|                  92.5%                    85.3%        |           84.5%                    86.0%           |
|TERMINAL (d)       |                  29/30 (97%)              18/22 (82%)  |           29/35 (83%)              33/40 (83%)     |
|FIRST INCIDENCE    |                  450                      365          |           519                      62              |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.242      |                                    P=0.362N        |
|POLY 3             |                                           P=0.192N     |                                    P=0.528         |
|POLY 1.5           |                                           P=0.227N     |                                    P=0.471         |
|POLY 6             |                                           P=0.155N     |                                    P=0.598         |
|LOGISTIC REGRESSION|                                           P=0.276N     |                                    P=0.393         |
|COCH-ARM / FISHERS |                                           P=0.277N     |                                    P=0.393         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 14
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Nephropathy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  49/50 (98%)              50/50 (100%) |           41/50 (82%)              44/50 (88%)     |
|POLY-3 ADJUSTED (b)|                  99.1%                    100.0%       |           87.3%                    90.0%           |
|TERMINAL (d)       |                  30/30 (100%)             22/22 (100%) |           34/35 (97%)              36/40 (90%)     |
|FIRST INCIDENCE    |                  450                      365          |           588                      491             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.076      |                                    P=0.383N        |
|POLY 3             |                                           P=0.901      |                                    P=0.459         |
|POLY 1.5           |                                           P=0.695      |                                    P=0.334         |
|POLY 6             |                                           P=1.000      |                                    P=0.629N        |
|LOGISTIC REGRESSION|                                           P=0.407      |                                    P=0.439         |
|COCH-ARM / FISHERS |                                           P=0.500      |                                    P=0.288         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Pigmentation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  3/50 (6%)                2/50 (4%)    |           2/50 (4%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  6.7%                     4.8%         |           4.4%                     2.1%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  450                      660          |           650                      652             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.539N     |                                    P=0.458N        |
|POLY 3             |                                           P=0.533N     |                                    P=0.482N        |
|POLY 1.5           |                                           P=0.519N     |                                    P=0.493N        |
|POLY 6             |                                           P=0.552N     |                                    P=0.467N        |
|LOGISTIC REGRESSION|                                           P=0.438N     |                                    P=0.490N        |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    P=0.500N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 15
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                2/50 (4%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     4.7%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      610          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.230      |                                    (e)             |
|POLY 3             |                                           P=0.234      |                                    (e)             |
|POLY 1.5           |                                           P=0.235      |                                    (e)             |
|POLY 6             |                                           P=0.232      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.258      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.247      |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                5/50 (10%)   |           0/50 (0%)                3/50 (6%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     12.0%        |           0.0%                     6.4%            |
|TERMINAL (d)       |                  0/30 (0%)                4/22 (18%)   |           0/35 (0%)                3/40 (8%)       |
|FIRST INCIDENCE    |                  ---                      674          |           ---                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.015 *    |                                    P=0.146         |
|POLY 3             |                                           P=0.027 *    |                                    P=0.124         |
|POLY 1.5           |                                           P=0.029 *    |                                    P=0.121         |
|POLY 6             |                                           P=0.025 *    |                                    P=0.128         |
|LOGISTIC REGRESSION|                                           P=0.022 *    |                                    P=0.146         |
|COCH-ARM / FISHERS |                                           P=0.028 *    |                                    P=0.121         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 16
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Basophilic Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  33/50 (66%)              24/50 (48%)  |           42/50 (84%)              48/50 (96%)     |
|POLY-3 ADJUSTED (b)|                  72.2%                    54.8%        |           89.6%                    98.5%           |
|TERMINAL (d)       |                  27/30 (90%)              18/22 (82%)  |           34/35 (97%)              40/40 (100%)    |
|FIRST INCIDENCE    |                  505                      532          |           588                      491             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.409N     |                                    P=0.554         |
|POLY 3             |                                           P=0.057N     |                                    P=0.040 *       |
|POLY 1.5           |                                           P=0.055N     |                                    P=0.027 *       |
|POLY 6             |                                           P=0.061N     |                                    P=0.089         |
|LOGISTIC REGRESSION|                                           P=0.077N     |                                    P=0.087         |
|COCH-ARM / FISHERS |                                           P=0.053N     |                                    P=0.046 *       |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Clear Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  14/50 (28%)              7/50 (14%)   |           0/50 (0%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  32.2%                    16.8%        |           0.0%                     2.1%            |
|TERMINAL (d)       |                  14/30 (47%)              7/22 (32%)   |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  726 (T)                  726 (T)      |           ---                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.216N     |                                    P=0.527         |
|POLY 3             |                                           P=0.078N     |                                    P=0.500         |
|POLY 1.5           |                                           P=0.074N     |                                    P=0.500         |
|POLY 6             |                                           P=0.086N     |                                    P=0.501         |
|LOGISTIC REGRESSION|                                           P=0.216N     |                                    P=0.527         |
|COCH-ARM / FISHERS |                                           P=0.070N     |                                    P=0.500         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 17
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Degeneration Cystic                                                                                                         |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  3/50 (6%)                2/50 (4%)    |           1/50 (2%)                2/50 (4%)       |
|POLY-3 ADJUSTED (b)|                  6.9%                     4.8%         |           2.2%                     4.2%            |
|TERMINAL (d)       |                  2/30 (7%)                1/22 (5%)    |           1/35 (3%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  639                      688          |           732 (T)                  697             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.599N     |                                    P=0.545         |
|POLY 3             |                                           P=0.526N     |                                    P=0.510         |
|POLY 1.5           |                                           P=0.515N     |                                    P=0.504         |
|POLY 6             |                                           P=0.544N     |                                    P=0.520         |
|LOGISTIC REGRESSION|                                           P=0.525N     |                                    P=0.516         |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    P=0.500         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Eosinophilic Focus                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  6/50 (12%)               3/50 (6%)    |           8/50 (16%)               8/50 (16%)      |
|POLY-3 ADJUSTED (b)|                  13.8%                    7.2%         |           17.7%                    17.0%           |
|TERMINAL (d)       |                  6/30 (20%)               3/22 (14%)   |           7/35 (20%)               8/40 (20%)      |
|FIRST INCIDENCE    |                  726 (T)                  726 (T)      |           719                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.411N     |                                    P=0.499N        |
|POLY 3             |                                           P=0.265N     |                                    P=0.572N        |
|POLY 1.5           |                                           P=0.255N     |                                    P=0.594N        |
|POLY 6             |                                           P=0.281N     |                                    P=0.542N        |
|LOGISTIC REGRESSION|                                           P=0.411N     |                                    P=0.518N        |
|COCH-ARM / FISHERS |                                           P=0.243N     |                                    P=0.607N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 18
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Fatty Change                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                4/50 (8%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  4.5%                     9.3%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                1/22 (5%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  505                      365          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.311      |                                    (e)             |
|POLY 3             |                                           P=0.325      |                                    (e)             |
|POLY 1.5           |                                           P=0.331      |                                    (e)             |
|POLY 6             |                                           P=0.316      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.444      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.339      |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hematopoietic Cell Proliferation                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                3/50 (6%)    |           1/50 (2%)                3/50 (6%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     7.0%         |           2.2%                     6.2%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      365          |           719                      62              |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.106      |                                    P=0.330         |
|POLY 3             |                                           P=0.117      |                                    P=0.324         |
|POLY 1.5           |                                           P=0.118      |                                    P=0.316         |
|POLY 6             |                                           P=0.114      |                                    P=0.335         |
|LOGISTIC REGRESSION|                                           P=0.166      |                                    P=0.394         |
|COCH-ARM / FISHERS |                                           P=0.121      |                                    P=0.309         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 19
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatodiaphragmatic Nodule                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  6/50 (12%)               3/50 (6%)    |           10/50 (20%)              8/50 (16%)      |
|POLY-3 ADJUSTED (b)|                  13.7%                    7.0%         |           21.7%                    16.6%           |
|TERMINAL (d)       |                  5/30 (17%)               0/22 (0%)    |           8/35 (23%)               5/40 (13%)      |
|FIRST INCIDENCE    |                  674                      509          |           508                      491             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.348N     |                                    P=0.304N        |
|POLY 3             |                                           P=0.247N     |                                    P=0.355N        |
|POLY 1.5           |                                           P=0.246N     |                                    P=0.381N        |
|POLY 6             |                                           P=0.253N     |                                    P=0.321N        |
|LOGISTIC REGRESSION|                                           P=0.224N     |                                    P=0.398N        |
|COCH-ARM / FISHERS |                                           P=0.243N     |                                    P=0.398N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  21/50 (42%)              22/50 (44%)  |           40/50 (80%)              44/50 (88%)     |
|POLY-3 ADJUSTED (b)|                  46.8%                    49.2%        |           86.1%                    90.3%           |
|TERMINAL (d)       |                  18/30 (60%)              16/22 (73%)  |           33/35 (94%)              36/40 (90%)     |
|FIRST INCIDENCE    |                  505                      365          |           588                      491             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.125      |                                    P=0.483N        |
|POLY 3             |                                           P=0.493      |                                    P=0.358         |
|POLY 1.5           |                                           P=0.499      |                                    P=0.243         |
|POLY 6             |                                           P=0.472      |                                    P=0.566         |
|LOGISTIC REGRESSION|                                           P=0.456      |                                    P=0.428         |
|COCH-ARM / FISHERS |                                           P=0.500      |                                    P=0.207         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 20
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Mixed Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  5/50 (10%)               1/50 (2%)    |           16/50 (32%)              18/50 (36%)     |
|POLY-3 ADJUSTED (b)|                  11.5%                    2.4%         |           35.4%                    38.2%           |
|TERMINAL (d)       |                  5/30 (17%)               1/22 (5%)    |           15/35 (43%)              18/40 (45%)     |
|FIRST INCIDENCE    |                  726 (T)                  726 (T)      |           719                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.183N     |                                    P=0.570N        |
|POLY 3             |                                           P=0.112N     |                                    P=0.470         |
|POLY 1.5           |                                           P=0.108N     |                                    P=0.435         |
|POLY 6             |                                           P=0.120N     |                                    P=0.518         |
|LOGISTIC REGRESSION|                                           P=0.183N     |                                    P=0.571         |
|COCH-ARM / FISHERS |                                           P=0.102N     |                                    P=0.417         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Vacuolization Cytoplasmic                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  7/50 (14%)               6/50 (12%)   |           5/50 (10%)               12/50 (24%)     |
|POLY-3 ADJUSTED (b)|                  16.1%                    14.3%        |           11.0%                    25.4%           |
|TERMINAL (d)       |                  7/30 (23%)               5/22 (23%)   |           3/35 (9%)                11/40 (28%)     |
|FIRST INCIDENCE    |                  726 (T)                  660          |           622                      697             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.516      |                                    P=0.098         |
|POLY 3             |                                           P=0.531N     |                                    P=0.060         |
|POLY 1.5           |                                           P=0.518N     |                                    P=0.055         |
|POLY 6             |                                           P=0.552N     |                                    P=0.068         |
|LOGISTIC REGRESSION|                                           P=0.601      |                                    P=0.071         |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    P=0.054         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 21
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Bile Duct                                                                                                                 |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  48/50 (96%)              45/50 (90%)  |           25/50 (50%)              15/50 (30%)     |
|POLY-3 ADJUSTED (b)|                  96.0%                    95.2%        |           52.0%                    30.9%           |
|TERMINAL (d)       |                  28/30 (93%)              22/22 (100%) |           15/35 (43%)              11/40 (28%)     |
|FIRST INCIDENCE    |                  450                      532          |           519                      62              |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.210      |                                    P=0.022N*       |
|POLY 3             |                                           P=0.639N     |                                    P=0.026N*       |
|POLY 1.5           |                                           P=0.449N     |                                    P=0.028N*       |
|POLY 6             |                                           P=0.637      |                                    P=0.024N*       |
|LOGISTIC REGRESSION|                                           P=0.302N     |                                    P=0.037N*       |
|COCH-ARM / FISHERS |                                           P=0.218N     |                                    P=0.033N*       |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Centrilobular                                                                                                             |
|     Degeneration                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  22/50 (44%)              19/50 (38%)  |           5/50 (10%)               6/50 (12%)      |
|POLY-3 ADJUSTED (b)|                  45.5%                    41.4%        |           10.7%                    12.6%           |
|TERMINAL (d)       |                  6/30 (20%)               2/22 (9%)    |           0/35 (0%)                4/40 (10%)      |
|FIRST INCIDENCE    |                  450                      446          |           595                      652             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.543N     |                                    P=0.583         |
|POLY 3             |                                           P=0.425N     |                                    P=0.509         |
|POLY 1.5           |                                           P=0.392N     |                                    P=0.500         |
|POLY 6             |                                           P=0.470N     |                                    P=0.519         |
|LOGISTIC REGRESSION|                                           P=0.266N     |                                    P=0.509         |
|COCH-ARM / FISHERS |                                           P=0.342N     |                                    P=0.500         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 22
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Hemorrhage                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  6/50 (12%)               2/50 (4%)    |           2/50 (4%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  13.7%                    4.8%         |           4.3%                     0.0%            |
|TERMINAL (d)       |                  4/30 (13%)               2/22 (9%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  660                      726 (T)      |           508                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.230N     |                                    P=0.242N        |
|POLY 3             |                                           P=0.152N     |                                    P=0.232N        |
|POLY 1.5           |                                           P=0.144N     |                                    P=0.237N        |
|POLY 6             |                                           P=0.167N     |                                    P=0.225N        |
|LOGISTIC REGRESSION|                                           P=0.165N     |                                    P=0.149N        |
|COCH-ARM / FISHERS |                                           P=0.134N     |                                    P=0.247N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  12/50 (24%)              12/50 (24%)  |           9/50 (18%)               7/50 (14%)      |
|POLY-3 ADJUSTED (b)|                  26.9%                    27.4%        |           19.9%                    14.9%           |
|TERMINAL (d)       |                  8/30 (27%)               5/22 (23%)   |           7/35 (20%)               7/40 (18%)      |
|FIRST INCIDENCE    |                  617                      365          |           719                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.384      |                                    P=0.293N        |
|POLY 3             |                                           P=0.578      |                                    P=0.358N        |
|POLY 1.5           |                                           P=0.585      |                                    P=0.380N        |
|POLY 6             |                                           P=0.562      |                                    P=0.329N        |
|LOGISTIC REGRESSION|                                           P=0.588      |                                    P=0.302N        |
|COCH-ARM / FISHERS |                                           P=0.592N     |                                    P=0.393N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 23
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/50 (2%)                3/50 (6%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  2.3%                     7.0%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  712                      365          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.280      |                                    (e)             |
|POLY 3             |                                           P=0.303      |                                    (e)             |
|POLY 1.5           |                                           P=0.304      |                                    (e)             |
|POLY 6             |                                           P=0.299      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.395      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.309      |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung: Alveolar Epithelium                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  7/50 (14%)               6/50 (12%)   |           9/50 (18%)               10/50 (20%)     |
|POLY-3 ADJUSTED (b)|                  16.0%                    14.0%        |           19.9%                    21.2%           |
|TERMINAL (d)       |                  6/30 (20%)               2/22 (9%)    |           8/35 (23%)               10/40 (25%)     |
|FIRST INCIDENCE    |                  674                      532          |           722                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.572      |                                    P=0.577N        |
|POLY 3             |                                           P=0.512N     |                                    P=0.537         |
|POLY 1.5           |                                           P=0.508N     |                                    P=0.513         |
|POLY 6             |                                           P=0.520N     |                                    P=0.568         |
|LOGISTIC REGRESSION|                                           P=0.519N     |                                    P=0.604         |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    P=0.500         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 24
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mandibular                                                                                                           |
|     Ectasia                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  4/50 (8%)                3/49 (6%)    |           0/50 (0%)                10/50 (20%)     |
|POLY-3 ADJUSTED (b)|                  9.1%                     7.3%         |           0.0%                     21.0%           |
|TERMINAL (d)       |                  3/30 (10%)               3/22 (14%)   |           0/35 (0%)                7/40 (18%)      |
|FIRST INCIDENCE    |                  639                      726 (T)      |           ---                      652             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.647N     |                                    P=0.003 **      |
|POLY 3             |                                           P=0.542N     |                                    P<0.001 **      |
|POLY 1.5           |                                           P=0.529N     |                                    P<0.001 **      |
|POLY 6             |                                           P=0.562N     |                                    P<0.001 **      |
|LOGISTIC REGRESSION|                                           P=0.567N     |                                    P<0.001 **      |
|COCH-ARM / FISHERS |                                           P=0.511N     |                                    P<0.001 **      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mandibular                                                                                                           |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  17/50 (34%)              14/49 (29%)  |           6/50 (12%)               17/50 (34%)     |
|POLY-3 ADJUSTED (b)|                  37.1%                    31.9%        |           13.2%                    35.8%           |
|TERMINAL (d)       |                  10/30 (33%)              7/22 (32%)   |           5/35 (14%)               14/40 (35%)     |
|FIRST INCIDENCE    |                  505                      509          |           635                      652             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.574N     |                                    P=0.023 *       |
|POLY 3             |                                           P=0.385N     |                                    P=0.009 **      |
|POLY 1.5           |                                           P=0.375N     |                                    P=0.008 **      |
|POLY 6             |                                           P=0.402N     |                                    P=0.012 *       |
|LOGISTIC REGRESSION|                                           P=0.340N     |                                    P=0.012 *       |
|COCH-ARM / FISHERS |                                           P=0.358N     |                                    P=0.008 **      |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 25
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mediastinal                                                                                                          |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                2/50 (4%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     4.8%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      688          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.199      |                                    (e)             |
|POLY 3             |                                           P=0.233      |                                    (e)             |
|POLY 1.5           |                                           P=0.235      |                                    (e)             |
|POLY 6             |                                           P=0.230      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.226      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.247      |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mesenteric                                                                                                           |
|     Ectasia                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  3/50 (6%)                1/50 (2%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  6.9%                     2.4%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  3/30 (10%)               0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  726 (T)                  509          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.391N     |                                    (e)             |
|POLY 3             |                                           P=0.317N     |                                    (e)             |
|POLY 1.5           |                                           P=0.312N     |                                    (e)             |
|POLY 6             |                                           P=0.327N     |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.295N     |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.309N     |                                    (e)             |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 26
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Galactocele                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                0/50 (0%)    |           3/50 (6%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     0.0%         |           6.5%                     2.1%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           1/35 (3%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  ---                      ---          |           627                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           (e)          |                                    P=0.264N        |
|POLY 3             |                                           (e)          |                                    P=0.294N        |
|POLY 1.5           |                                           (e)          |                                    P=0.302N        |
|POLY 6             |                                           (e)          |                                    P=0.284N        |
|LOGISTIC REGRESSION|                                           (e)          |                                    P=0.300N        |
|COCH-ARM / FISHERS |                                           (e)          |                                    P=0.309N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  3/50 (6%)                7/50 (14%)   |           0/50 (0%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  6.9%                     16.5%        |           0.0%                     2.1%            |
|TERMINAL (d)       |                  2/30 (7%)                3/22 (14%)   |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  674                      660          |           ---                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.094      |                                    P=0.527         |
|POLY 3             |                                           P=0.144      |                                    P=0.500         |
|POLY 1.5           |                                           P=0.150      |                                    P=0.500         |
|POLY 6             |                                           P=0.136      |                                    P=0.501         |
|LOGISTIC REGRESSION|                                           P=0.134      |                                    P=0.527         |
|COCH-ARM / FISHERS |                                           P=0.159      |                                    P=0.500         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 27
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                0/50 (0%)    |           4/50 (8%)                5/50 (10%)      |
|POLY-3 ADJUSTED (b)|                  0.0%                     0.0%         |           8.8%                     10.6%           |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           3/35 (9%)                5/40 (13%)      |
|FIRST INCIDENCE    |                  ---                      ---          |           719                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           (e)          |                                    P=0.576         |
|POLY 3             |                                           (e)          |                                    P=0.522         |
|POLY 1.5           |                                           (e)          |                                    P=0.508         |
|POLY 6             |                                           (e)          |                                    P=0.541         |
|LOGISTIC REGRESSION|                                           (e)          |                                    P=0.568         |
|COCH-ARM / FISHERS |                                           (e)          |                                    P=0.500         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery                                                                                                                        |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/8 (0%)                 1/13 (8%)    |           0/10 (0%)                2/5 (40%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     9.3%         |           0.0%                     40.8%           |
|TERMINAL (d)       |                  0/4 (0%)                 0/3 (0%)     |           0/8 (0%)                 1/3 (33%)       |
|FIRST INCIDENCE    |                  ---                      707          |           ---                      652             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.457      |                                    P=0.149         |
|POLY 3             |                                           P=0.495      |                                    P=0.115         |
|POLY 1.5           |                                           P=0.497      |                                    P=0.114         |
|POLY 6             |                                           P=0.492      |                                    P=0.115         |
|LOGISTIC REGRESSION|                                           P=0.549      |                                    P=0.080         |
|COCH-ARM / FISHERS |                                           P=0.619      |                                    P=0.095         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 28
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery: Fat                                                                                                                   |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  7/8 (88%)                11/13 (85%)  |           8/10 (80%)               3/5 (60%)       |
|POLY-3 ADJUSTED (b)|                  88.1%                    85.6%        |           86.3%                    63.7%           |
|TERMINAL (d)       |                  4/4 (100%)               3/3 (100%)   |           8/8 (100%)               2/3 (67%)       |
|FIRST INCIDENCE    |                  610                      532          |           732 (T)                  708             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.088      |                                    P=0.636N        |
|POLY 3             |                                           P=0.630N     |                                    P=0.473N        |
|POLY 1.5           |                                           P=0.622N     |                                    P=0.486N        |
|POLY 6             |                                           P=0.646N     |                                    P=0.455N        |
|LOGISTIC REGRESSION|                                           P=0.579N     |                                    P=0.455N        |
|COCH-ARM / FISHERS |                                           P=0.684N     |                                    P=0.407N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Foreign Body                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  7/50 (14%)               7/50 (14%)   |           3/50 (6%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  15.6%                    16.5%        |           6.6%                     2.1%            |
|TERMINAL (d)       |                  3/30 (10%)               4/22 (18%)   |           3/35 (9%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  505                      610          |           732 (T)                  732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.468      |                                    P=0.258N        |
|POLY 3             |                                           P=0.573      |                                    P=0.287N        |
|POLY 1.5           |                                           P=0.589      |                                    P=0.299N        |
|POLY 6             |                                           P=0.547      |                                    P=0.273N        |
|LOGISTIC REGRESSION|                                           P=0.612N     |                                    P=0.258N        |
|COCH-ARM / FISHERS |                                           P=0.613N     |                                    P=0.309N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 29
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  13/50 (26%)              11/50 (22%)  |           4/50 (8%)                5/50 (10%)      |
|POLY-3 ADJUSTED (b)|                  28.1%                    24.8%        |           8.8%                     10.6%           |
|TERMINAL (d)       |                  5/30 (17%)               3/22 (14%)   |           3/35 (9%)                3/40 (8%)       |
|FIRST INCIDENCE    |                  505                      446          |           719                      708             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.563N     |                                    P=0.566         |
|POLY 3             |                                           P=0.454N     |                                    P=0.524         |
|POLY 1.5           |                                           P=0.434N     |                                    P=0.509         |
|POLY 6             |                                           P=0.490N     |                                    P=0.545         |
|LOGISTIC REGRESSION|                                           P=0.339N     |                                    P=0.557         |
|COCH-ARM / FISHERS |                                           P=0.408N     |                                    P=0.500         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |           3/50 (6%)                11/50 (22%)     |
|POLY-3 ADJUSTED (b)|                                                        |           6.6%                     23.0%           |
|TERMINAL (d)       |                                                        |           1/35 (3%)                8/40 (20%)      |
|FIRST INCIDENCE    |                                                        |           636                      652             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |                                    P=0.047 *       |
|POLY 3             |                                                        |                                    P=0.024 *       |
|POLY 1.5           |                                                        |                                    P=0.021 *       |
|POLY 6             |                                                        |                                    P=0.029 *       |
|LOGISTIC REGRESSION|                                                        |                                    P=0.022 *       |
|COCH-ARM / FISHERS |                                                        |                                    P=0.020 *       |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 30
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  22/50 (44%)              18/50 (36%)  |           8/50 (16%)               12/50 (24%)     |
|POLY-3 ADJUSTED (b)|                  48.2%                    40.5%        |           17.6%                    25.1%           |
|TERMINAL (d)       |                  15/30 (50%)              9/22 (41%)   |           7/35 (20%)               8/40 (20%)      |
|FIRST INCIDENCE    |                  450                      365          |           627                      652             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.548      |                                    P=0.343         |
|POLY 3             |                                           P=0.298N     |                                    P=0.261         |
|POLY 1.5           |                                           P=0.287N     |                                    P=0.239         |
|POLY 6             |                                           P=0.317N     |                                    P=0.294         |
|LOGISTIC REGRESSION|                                           P=0.286N     |                                    P=0.244         |
|COCH-ARM / FISHERS |                                           P=0.270N     |                                    P=0.227         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                0/50 (0%)    |           0/50 (0%)                2/50 (4%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     0.0%         |           0.0%                     4.2%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  ---                      ---          |           ---                      652             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           (e)          |                                    P=0.275         |
|POLY 3             |                                           (e)          |                                    P=0.243         |
|POLY 1.5           |                                           (e)          |                                    P=0.239         |
|POLY 6             |                                           (e)          |                                    P=0.248         |
|LOGISTIC REGRESSION|                                           (e)          |                                    P=0.238         |
|COCH-ARM / FISHERS |                                           (e)          |                                    P=0.247         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 31
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Cytoplasmic Alteration                                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/50 (2%)                2/50 (4%)    |           2/50 (4%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  2.3%                     4.8%         |           4.4%                     2.1%            |
|TERMINAL (d)       |                  1/30 (3%)                2/22 (9%)    |           1/35 (3%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  726 (T)                  726 (T)      |           719                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.392      |                                    P=0.466N        |
|POLY 3             |                                           P=0.490      |                                    P=0.482N        |
|POLY 1.5           |                                           P=0.494      |                                    P=0.493N        |
|POLY 6             |                                           P=0.484      |                                    P=0.467N        |
|LOGISTIC REGRESSION|                                           P=0.392      |                                    P=0.465N        |
|COCH-ARM / FISHERS |                                           P=0.500      |                                    P=0.500N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  3/50 (6%)                2/50 (4%)    |           1/50 (2%)                2/50 (4%)       |
|POLY-3 ADJUSTED (b)|                  6.9%                     4.8%         |           2.2%                     4.2%            |
|TERMINAL (d)       |                  3/30 (10%)               2/22 (9%)    |           1/35 (3%)                2/40 (5%)       |
|FIRST INCIDENCE    |                  726 (T)                  726 (T)      |           732 (T)                  732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.642N     |                                    P=0.547         |
|POLY 3             |                                           P=0.524N     |                                    P=0.510         |
|POLY 1.5           |                                           P=0.514N     |                                    P=0.503         |
|POLY 6             |                                           P=0.541N     |                                    P=0.518         |
|LOGISTIC REGRESSION|                                           P=0.642N     |                                    P=0.547         |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    P=0.500         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 32
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                1/50 (2%)    |           1/50 (2%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  4.6%                     2.4%         |           2.2%                     0.0%            |
|TERMINAL (d)       |                  2/30 (7%)                1/22 (5%)    |           1/35 (3%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  726 (T)                  726 (T)      |           732 (T)                  ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.608N     |                                    P=0.473N        |
|POLY 3             |                                           P=0.520N     |                                    P=0.484N        |
|POLY 1.5           |                                           P=0.512N     |                                    P=0.494N        |
|POLY 6             |                                           P=0.535N     |                                    P=0.471N        |
|LOGISTIC REGRESSION|                                           P=0.608N     |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    P=0.500N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland                                                                                                                  |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  5/50 (10%)               4/50 (8%)    |           1/50 (2%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  11.4%                    9.4%         |           2.2%                     0.0%            |
|TERMINAL (d)       |                  3/30 (10%)               2/22 (9%)    |           1/35 (3%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  660                      509          |           732 (T)                  ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.618N     |                                    P=0.473N        |
|POLY 3             |                                           P=0.521N     |                                    P=0.484N        |
|POLY 1.5           |                                           P=0.512N     |                                    P=0.494N        |
|POLY 6             |                                           P=0.539N     |                                    P=0.471N        |
|LOGISTIC REGRESSION|                                           P=0.496N     |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    P=0.500N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 33
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  15/50 (30%)              22/50 (44%)  |           27/50 (54%)              29/50 (58%)     |
|POLY-3 ADJUSTED (b)|                  33.6%                    49.2%        |           56.8%                    59.5%           |
|TERMINAL (d)       |                  11/30 (37%)              10/22 (46%)  |           20/35 (57%)              22/40 (55%)     |
|FIRST INCIDENCE    |                  589                      532          |           588                      491             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.032 *    |                                    P=0.469N        |
|POLY 3             |                                           P=0.095      |                                    P=0.472         |
|POLY 1.5           |                                           P=0.098      |                                    P=0.433         |
|POLY 6             |                                           P=0.093      |                                    P=0.520         |
|LOGISTIC REGRESSION|                                           P=0.084      |                                    P=0.430         |
|COCH-ARM / FISHERS |                                           P=0.107      |                                    P=0.420         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                2/50 (4%)    |                                                    |
|POLY-3 ADJUSTED (b)|                  4.6%                     4.8%         |                                                    |
|TERMINAL (d)       |                  1/30 (3%)                1/22 (5%)    |                                                    |
|FIRST INCIDENCE    |                  695                      695          |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.605      |                                                    |
|POLY 3             |                                           P=0.683      |                                                    |
|POLY 1.5           |                                           P=0.687      |                                                    |
|POLY 6             |                                           P=0.676      |                                                    |
|LOGISTIC REGRESSION|                                           P=0.661      |                                                    |
|COCH-ARM / FISHERS |                                           P=0.691N     |                                                    |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 34
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  47/50 (94%)              48/50 (96%)  |                                                    |
|POLY-3 ADJUSTED (b)|                  94.7%                    97.7%        |                                                    |
|TERMINAL (d)       |                  28/30 (93%)              21/22 (96%)  |                                                    |
|FIRST INCIDENCE    |                  450                      446          |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.089      |                                                    |
|POLY 3             |                                           P=0.400      |                                                    |
|POLY 1.5           |                                           P=0.416      |                                                    |
|POLY 6             |                                           P=0.422      |                                                    |
|LOGISTIC REGRESSION|                                           P=0.440      |                                                    |
|COCH-ARM / FISHERS |                                           P=0.500      |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  4/50 (8%)                1/50 (2%)    |                                                    |
|POLY-3 ADJUSTED (b)|                  9.0%                     2.4%         |                                                    |
|TERMINAL (d)       |                  1/30 (3%)                0/22 (0%)    |                                                    |
|FIRST INCIDENCE    |                  589                      637          |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.218N     |                                                    |
|POLY 3             |                                           P=0.200N     |                                                    |
|POLY 1.5           |                                           P=0.191N     |                                                    |
|POLY 6             |                                           P=0.216N     |                                                    |
|LOGISTIC REGRESSION|                                           P=0.153N     |                                                    |
|COCH-ARM / FISHERS |                                           P=0.181N     |                                                    |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 35
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                3/50 (6%)    |                                                    |
|POLY-3 ADJUSTED (b)|                  4.6%                     7.2%         |                                                    |
|TERMINAL (d)       |                  2/30 (7%)                3/22 (14%)   |                                                    |
|FIRST INCIDENCE    |                  726 (T)                  726 (T)      |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.358      |                                                    |
|POLY 3             |                                           P=0.484      |                                                    |
|POLY 1.5           |                                           P=0.491      |                                                    |
|POLY 6             |                                           P=0.474      |                                                    |
|LOGISTIC REGRESSION|                                           P=0.358      |                                                    |
|COCH-ARM / FISHERS |                                           P=0.500      |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  22/50 (44%)              33/50 (66%)  |                                                    |
|POLY-3 ADJUSTED (b)|                  46.9%                    70.9%        |                                                    |
|TERMINAL (d)       |                  14/30 (47%)              18/22 (82%)  |                                                    |
|FIRST INCIDENCE    |                  450                      365          |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.005 **   |                                                    |
|POLY 3             |                                           P=0.012 *    |                                                    |
|POLY 1.5           |                                           P=0.015 *    |                                                    |
|POLY 6             |                                           P=0.009 **   |                                                    |
|LOGISTIC REGRESSION|                                           P=0.023 *    |                                                    |
|COCH-ARM / FISHERS |                                           P=0.022 *    |                                                    |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 36
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Salivary Glands                                                                                                                  |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/50 (2%)                1/50 (2%)    |           2/50 (4%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  2.3%                     2.4%         |           4.4%                     0.0%            |
|TERMINAL (d)       |                  1/30 (3%)                0/22 (0%)    |           1/35 (3%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  726 (T)                  532          |           588                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.724      |                                    P=0.225N        |
|POLY 3             |                                           P=0.758      |                                    P=0.227N        |
|POLY 1.5           |                                           P=0.759      |                                    P=0.234N        |
|POLY 6             |                                           P=0.756      |                                    P=0.218N        |
|LOGISTIC REGRESSION|                                           P=0.735N     |                                    P=0.222N        |
|COCH-ARM / FISHERS |                                           P=0.753N     |                                    P=0.247N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Salivary Glands                                                                                                                  |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                0/50 (0%)    |           0/50 (0%)                2/50 (4%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     0.0%         |           0.0%                     4.2%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  ---                      ---          |           ---                      687             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           (e)          |                                    P=0.273         |
|POLY 3             |                                           (e)          |                                    P=0.243         |
|POLY 1.5           |                                           (e)          |                                    P=0.239         |
|POLY 6             |                                           (e)          |                                    P=0.247         |
|LOGISTIC REGRESSION|                                           (e)          |                                    P=0.238         |
|COCH-ARM / FISHERS |                                           (e)          |                                    P=0.247         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 37
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Hyperkeratosis                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                4/50 (8%)    |           1/50 (2%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     9.5%         |           2.2%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                3/22 (14%)   |           1/35 (3%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      639          |           732 (T)                  ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.037 *    |                                    P=0.473N        |
|POLY 3             |                                           P=0.056      |                                    P=0.484N        |
|POLY 1.5           |                                           P=0.058      |                                    P=0.494N        |
|POLY 6             |                                           P=0.054      |                                    P=0.471N        |
|LOGISTIC REGRESSION|                                           P=0.054      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.059      |                                    P=0.500N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                3/50 (6%)    |           1/50 (2%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     7.2%         |           2.2%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                3/22 (14%)   |           1/35 (3%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      726 (T)      |           732 (T)                  ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.071      |                                    P=0.473N        |
|POLY 3             |                                           P=0.113      |                                    P=0.484N        |
|POLY 1.5           |                                           P=0.116      |                                    P=0.494N        |
|POLY 6             |                                           P=0.109      |                                    P=0.471N        |
|LOGISTIC REGRESSION|                                           P=0.071      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.121      |                                    P=0.500N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 38
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Epidermis                                                                                                                  |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                1/50 (2%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  4.6%                     2.4%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  1/30 (3%)                1/22 (5%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  653                      726 (T)      |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.577N     |                                    (e)             |
|POLY 3             |                                           P=0.523N     |                                    (e)             |
|POLY 1.5           |                                           P=0.513N     |                                    (e)             |
|POLY 6             |                                           P=0.540N     |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.520N     |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Spinal Cord                                                                                                                      |
|     Hemorrhage                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/0 (0%)                 2/2 (100%)   |           0/0 (0%)                 0/0 (0%)        |
|POLY-3 ADJUSTED (b)|                  0.0%                     100.0%       |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/0 (0%)                 0/0 (0%)     |           0/0 (0%)                 0/0 (0%)        |
|FIRST INCIDENCE    |                  ---                      623          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           (e)          |                                    (e)             |
|POLY 3             |                                           (e)          |                                    (e)             |
|POLY 1.5           |                                           (e)          |                                    (e)             |
|POLY 6             |                                           (e)          |                                    (e)             |
|LOGISTIC REGRESSION|                                           (e)          |                                    (e)             |
|COCH-ARM / FISHERS |                                           (e)          |                                    (e)             |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 39
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Fibrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                2/50 (4%)    |           1/50 (2%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  4.6%                     4.8%         |           2.2%                     2.1%            |
|TERMINAL (d)       |                  2/30 (7%)                2/22 (9%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  726 (T)                  726 (T)      |           650                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.580      |                                    P=0.728N        |
|POLY 3             |                                           P=0.683      |                                    P=0.749N        |
|POLY 1.5           |                                           P=0.687      |                                    P=0.757N        |
|POLY 6             |                                           P=0.676      |                                    P=0.740N        |
|LOGISTIC REGRESSION|                                           P=0.580      |                                    P=0.762N        |
|COCH-ARM / FISHERS |                                           P=0.691N     |                                    P=0.753N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hematopoietic Cell Proliferation                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  3/50 (6%)                8/50 (16%)   |           11/50 (22%)              11/50 (22%)     |
|POLY-3 ADJUSTED (b)|                  6.8%                     17.9%        |           23.9%                    22.7%           |
|TERMINAL (d)       |                  2/30 (7%)                0/22 (0%)    |           7/35 (20%)               6/40 (15%)      |
|FIRST INCIDENCE    |                  610                      365          |           609                      62              |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.090      |                                    P=0.480N        |
|POLY 3             |                                           P=0.103      |                                    P=0.537N        |
|POLY 1.5           |                                           P=0.102      |                                    P=0.562N        |
|POLY 6             |                                           P=0.104      |                                    P=0.504N        |
|LOGISTIC REGRESSION|                                           P=0.137      |                                    P=0.594         |
|COCH-ARM / FISHERS |                                           P=0.100      |                                    P=0.595N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 40
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Infarct                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                2/50 (4%)    |           1/50 (2%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  4.6%                     4.8%         |           2.2%                     0.0%            |
|TERMINAL (d)       |                  1/30 (3%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  600                      674          |           650                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.630      |                                    P=0.469N        |
|POLY 3             |                                           P=0.682      |                                    P=0.487N        |
|POLY 1.5           |                                           P=0.687      |                                    P=0.495N        |
|POLY 6             |                                           P=0.674      |                                    P=0.475N        |
|LOGISTIC REGRESSION|                                           P=0.692N     |                                    P=0.484N        |
|COCH-ARM / FISHERS |                                           P=0.691N     |                                    P=0.500N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                2/50 (4%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     4.8%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      674          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.217      |                                    (e)             |
|POLY 3             |                                           P=0.233      |                                    (e)             |
|POLY 1.5           |                                           P=0.235      |                                    (e)             |
|POLY 6             |                                           P=0.231      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.240      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.247      |                                    (e)             |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 41
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen: Lymphoid Follicle                                                                                                        |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                2/50 (4%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     4.8%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      663          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.221      |                                    (e)             |
|POLY 3             |                                           P=0.233      |                                    (e)             |
|POLY 1.5           |                                           P=0.235      |                                    (e)             |
|POLY 6             |                                           P=0.231      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.242      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.247      |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Ulcer                                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/50 (2%)                3/50 (6%)    |           2/50 (4%)                0/49 (0%)       |
|POLY-3 ADJUSTED (b)|                  2.3%                     7.1%         |           4.3%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           0/35 (0%)                0/39 (0%)       |
|FIRST INCIDENCE    |                  695                      628          |           508                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.289      |                                    P=0.227N        |
|POLY 3             |                                           P=0.298      |                                    P=0.238N        |
|POLY 1.5           |                                           P=0.301      |                                    P=0.243N        |
|POLY 6             |                                           P=0.294      |                                    P=0.230N        |
|LOGISTIC REGRESSION|                                           P=0.328      |                                    P=0.171N        |
|COCH-ARM / FISHERS |                                           P=0.309      |                                    P=0.253N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 42
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach: Epithelium                                                                                                 |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/50 (2%)                6/50 (12%)   |           6/50 (12%)               1/49 (2%)       |
|POLY-3 ADJUSTED (b)|                  2.3%                     13.9%        |           12.6%                    2.2%            |
|TERMINAL (d)       |                  0/30 (0%)                1/22 (5%)    |           0/35 (0%)                0/39 (0%)       |
|FIRST INCIDENCE    |                  674                      532          |           508                      697             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.048 *    |                                    P=0.053N        |
|POLY 3             |                                           P=0.053      |                                    P=0.062N        |
|POLY 1.5           |                                           P=0.054      |                                    P=0.063N        |
|POLY 6             |                                           P=0.051      |                                    P=0.061N        |
|LOGISTIC REGRESSION|                                           P=0.066      |                                    P=0.040N*       |
|COCH-ARM / FISHERS |                                           P=0.056      |                                    P=0.059N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Erosion                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                7/50 (14%)   |           2/50 (4%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  4.6%                     16.3%        |           4.4%                     2.1%            |
|TERMINAL (d)       |                  0/30 (0%)                1/22 (5%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  674                      610          |           622                      715             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.062      |                                    P=0.477N        |
|POLY 3             |                                           P=0.074      |                                    P=0.488N        |
|POLY 1.5           |                                           P=0.076      |                                    P=0.497N        |
|POLY 6             |                                           P=0.071      |                                    P=0.477N        |
|LOGISTIC REGRESSION|                                           P=0.084      |                                    P=0.477N        |
|COCH-ARM / FISHERS |                                           P=0.080      |                                    P=0.500N        |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 43
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Ulcer                                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  3/50 (6%)                4/50 (8%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  6.8%                     9.5%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                1/22 (5%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  653                      660          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.425      |                                    (e)             |
|POLY 3             |                                           P=0.481      |                                    (e)             |
|POLY 1.5           |                                           P=0.489      |                                    (e)             |
|POLY 6             |                                           P=0.468      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.495      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.500      |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                2/50 (4%)    |                                                    |
|POLY-3 ADJUSTED (b)|                  4.6%                     4.7%         |                                                    |
|TERMINAL (d)       |                  1/30 (3%)                0/22 (0%)    |                                                    |
|FIRST INCIDENCE    |                  660                      637          |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.653      |                                                    |
|POLY 3             |                                           P=0.685      |                                                    |
|POLY 1.5           |                                           P=0.688      |                                                    |
|POLY 6             |                                           P=0.679      |                                                    |
|LOGISTIC REGRESSION|                                           P=0.686N     |                                                    |
|COCH-ARM / FISHERS |                                           P=0.691N     |                                                    |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 44
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes: Interstitial Cell                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  4/50 (8%)                7/50 (14%)   |                                                    |
|POLY-3 ADJUSTED (b)|                  8.8%                     16.0%        |                                                    |
|TERMINAL (d)       |                  1/30 (3%)                2/22 (9%)    |                                                    |
|FIRST INCIDENCE    |                  450                      365          |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.213      |                                                    |
|POLY 3             |                                           P=0.241      |                                                    |
|POLY 1.5           |                                           P=0.250      |                                                    |
|POLY 6             |                                           P=0.229      |                                                    |
|LOGISTIC REGRESSION|                                           P=0.357      |                                                    |
|COCH-ARM / FISHERS |                                           P=0.262      |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Thymus                                                                                                                           |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  45/50 (90%)              38/47 (81%)  |           45/49 (92%)              46/47 (98%)     |
|POLY-3 ADJUSTED (b)|                  93.3%                    84.9%        |           95.7%                    100.0%          |
|TERMINAL (d)       |                  30/30 (100%)             19/22 (86%)  |           35/35 (100%)             37/37 (100%)    |
|FIRST INCIDENCE    |                  450                      365          |           588                      491             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.435      |                                    P=0.423N        |
|POLY 3             |                                           P=0.139N     |                                    P=0.175         |
|POLY 1.5           |                                           P=0.152N     |                                    P=0.111         |
|POLY 6             |                                           P=0.118N     |                                    P=0.436         |
|LOGISTIC REGRESSION|                                           P=0.195N     |                                    P=0.109         |
|COCH-ARM / FISHERS |                                           P=0.161N     |                                    P=0.194         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 45
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  32/50 (64%)              38/50 (76%)  |           45/50 (90%)              45/50 (90%)     |
|POLY-3 ADJUSTED (b)|                  66.9%                    81.3%        |           92.2%                    91.8%           |
|TERMINAL (d)       |                  19/30 (63%)              18/22 (82%)  |           33/35 (94%)              36/40 (90%)     |
|FIRST INCIDENCE    |                  450                      509          |           519                      491             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.034 *    |                                    P=0.194N        |
|POLY 3             |                                           P=0.076      |                                    P=0.624N        |
|POLY 1.5           |                                           P=0.093      |                                    P=0.610         |
|POLY 6             |                                           P=0.065      |                                    P=0.542N        |
|LOGISTIC REGRESSION|                                           P=0.114      |                                    P=0.624         |
|COCH-ARM / FISHERS |                                           P=0.138      |                                    P=0.630N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/50 (2%)                2/50 (4%)    |           0/50 (0%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  2.3%                     4.8%         |           0.0%                     2.1%            |
|TERMINAL (d)       |                  1/30 (3%)                2/22 (9%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  726 (T)                  726 (T)      |           ---                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.392      |                                    P=0.527         |
|POLY 3             |                                           P=0.490      |                                    P=0.500         |
|POLY 1.5           |                                           P=0.494      |                                    P=0.500         |
|POLY 6             |                                           P=0.484      |                                    P=0.501         |
|LOGISTIC REGRESSION|                                           P=0.392      |                                    P=0.527         |
|COCH-ARM / FISHERS |                                           P=0.500      |                                    P=0.500         |
|=================================================================================================================================|

       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 46
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus: Endometrium                                                                                                              |
|     Hyperplasia Cystic                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |           9/50 (18%)               12/50 (24%)     |
|POLY-3 ADJUSTED (b)|                                                        |           19.5%                    25.3%           |
|TERMINAL (d)       |                                                        |           5/35 (14%)               10/40 (25%)     |
|FIRST INCIDENCE    |                                                        |           595                      687             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |                                    P=0.432         |
|POLY 3             |                                                        |                                    P=0.331         |
|POLY 1.5           |                                                        |                                    P=0.316         |
|POLY 6             |                                                        |                                    P=0.351         |
|LOGISTIC REGRESSION|                                                        |                                    P=0.324         |
|COCH-ARM / FISHERS |                                                        |                                    P=0.312         |
|=================================================================================================================================|
 
(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).