https://ntp.niehs.nih.gov/go/12915

TDMS Study 56348-03 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08
LAB: Battelle Columbus                                           CITRAL                                        DATE: 06/01/00
EXPERIMENT: 56348 TEST: 03                                                                                     TIME: 12:39:05
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
Rats(FISCHER 344)
-----------------------------
FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE
BASED ON NUMBER OF TISSUES EXAMINED.  IN OTHER TISSUES/ORGANS RATES
ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED.
                                                 ---------------
                                                 Adrenal Cortex
                                                 Adrenal Medulla
                                                 Brain
                                                 Clitoral/Preputial Gland
                                                 Heart
                                                 Islets, Pancreatic
                                                 Kidney
                                                 Lung
                                                 Nose
                                                 Pancreas
                                                 Parathyroid Gland
                                                 Pituitary Gland
                                                 Testes
                                                 Thyroid Gland
                                                 Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08   
LAB: Battelle Columbus                                           CITRAL                                        DATE: 06/01/00     
EXPERIMENT: 56348 TEST: 03                                                                                     TIME: 12:39:05     
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
-----                                 ----------
Thyroid Gland: Follicular Cell         Carcinoma or Adenoma
===============================================================
Female Rats
------------
Organ                                  Morphology
-----                                  ----------
Uterus                                 Polyp Stromal
===============================================================
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 1
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)        -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  6/50 (12%)               4/50 (8%)    |           2/49 (4%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  13.6%                    9.5%         |           4.5%                     2.1%            |
|TERMINAL (d)       |                  3/30 (10%)               2/22 (9%)    |           2/34 (6%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  639                      610          |           732 (T)                  708             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.491N     |                                    P=0.451N        |
|POLY 3             |                                           P=0.402N     |                                    P=0.470N        |
|POLY 1.5           |                                           P=0.388N     |                                    P=0.483N        |
|POLY 6             |                                           P=0.426N     |                                    P=0.453N        |
|LOGISTIC REGRESSION|                                           P=0.383N     |                                    P=0.465N        |
|COCH-ARM / FISHERS |                                           P=0.370N     |                                    P=0.492N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  7/50 (14%)               4/50 (8%)    |           2/49 (4%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  15.8%                    9.5%         |           4.5%                     2.1%            |
|TERMINAL (d)       |                  4/30 (13%)               2/22 (9%)    |           2/34 (6%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  639                      610          |           732 (T)                  708             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.387N     |                                    P=0.451N        |
|POLY 3             |                                           P=0.290N     |                                    P=0.470N        |
|POLY 1.5           |                                           P=0.278N     |                                    P=0.483N        |
|POLY 6             |                                           P=0.312N     |                                    P=0.453N        |
|LOGISTIC REGRESSION|                                           P=0.278N     |                                    P=0.465N        |
|COCH-ARM / FISHERS |                                           P=0.262N     |                                    P=0.492N        |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 2
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  4/50 (8%)                3/50 (6%)    |           9/49 (18%)               6/49 (12%)      |
|POLY-3 ADJUSTED (b)|                  9.2%                     7.1%         |           20.2%                    13.0%           |
|TERMINAL (d)       |                  3/30 (10%)               1/22 (5%)    |           8/35 (23%)               5/40 (13%)      |
|FIRST INCIDENCE    |                  660                      639          |           719                      708             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.612N     |                                    P=0.208N        |
|POLY 3             |                                           P=0.524N     |                                    P=0.259N        |
|POLY 1.5           |                                           P=0.514N     |                                    P=0.278N        |
|POLY 6             |                                           P=0.540N     |                                    P=0.235N        |
|LOGISTIC REGRESSION|                                           P=0.527N     |                                    P=0.218N        |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    P=0.288N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  5/50 (10%)               3/50 (6%)    |           9/49 (18%)               7/49 (14%)      |
|POLY-3 ADJUSTED (b)|                  11.3%                    7.1%         |           20.2%                    15.1%           |
|TERMINAL (d)       |                  3/30 (10%)               1/22 (5%)    |           8/35 (23%)               6/40 (15%)      |
|FIRST INCIDENCE    |                  617                      639          |           719                      708             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.458N     |                                    P=0.295N        |
|POLY 3             |                                           P=0.385N     |                                    P=0.359N        |
|POLY 1.5           |                                           P=0.373N     |                                    P=0.381N        |
|POLY 6             |                                           P=0.405N     |                                    P=0.331N        |
|LOGISTIC REGRESSION|                                           P=0.367N     |                                    P=0.309N        |
|COCH-ARM / FISHERS |                                           P=0.357N     |                                    P=0.393N        |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 3
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/49 (2%)                2/50 (4%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  2.3%                     4.8%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                2/22 (9%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  674                      726 (T)      |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.415      |                                    (e)             |
|POLY 3             |                                           P=0.493      |                                    (e)             |
|POLY 1.5           |                                           P=0.498      |                                    (e)             |
|POLY 6             |                                           P=0.485      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.474      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.508      |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR 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%)                2/40 (5%)       |
|FIRST INCIDENCE    |                  ---                      ---          |           ---                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           (e)          |                                    P=0.268         |
|POLY 3             |                                           (e)          |                                    P=0.242         |
|POLY 1.5           |                                           (e)          |                                    P=0.239         |
|POLY 6             |                                           (e)          |                                    P=0.246         |
|LOGISTIC REGRESSION|                                           (e)          |                                    P=0.268         |
|COCH-ARM / FISHERS |                                           (e)          |                                    P=0.247         |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 4
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                1/50 (2%)    |           1/50 (2%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  4.6%                     2.4%         |           2.2%                     2.1%            |
|TERMINAL (d)       |                  1/30 (3%)                0/22 (0%)    |           1/35 (3%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  695                      637          |           732 (T)                  694             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.558N     |                                    P=0.729N        |
|POLY 3             |                                           P=0.518N     |                                    P=0.746N        |
|POLY 1.5           |                                           P=0.510N     |                                    P=0.755N        |
|POLY 6             |                                           P=0.530N     |                                    P=0.734N        |
|LOGISTIC REGRESSION|                                           P=0.504N     |                                    P=0.761N        |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    P=0.753N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar                                                                      |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                1/50 (2%)    |           1/50 (2%)                2/50 (4%)       |
|POLY-3 ADJUSTED (b)|                  4.6%                     2.4%         |           2.2%                     4.2%            |
|TERMINAL (d)       |                  1/30 (3%)                0/22 (0%)    |           1/35 (3%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  695                      637          |           732 (T)                  694             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.558N     |                                    P=0.546         |
|POLY 3             |                                           P=0.518N     |                                    P=0.511         |
|POLY 1.5           |                                           P=0.510N     |                                    P=0.504         |
|POLY 6             |                                           P=0.530N     |                                    P=0.521         |
|LOGISTIC REGRESSION|                                           P=0.504N     |                                    P=0.501         |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    P=0.500         |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 5
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR 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%)                1/22 (5%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      695          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.189      |                                    (e)             |
|POLY 3             |                                           P=0.233      |                                    (e)             |
|POLY 1.5           |                                           P=0.235      |                                    (e)             |
|POLY 6             |                                           P=0.230      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.215      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.247      |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/50 (2%)                2/50 (4%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  2.3%                     4.8%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                1/22 (5%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  688                      695          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.431      |                                    (e)             |
|POLY 3             |                                           P=0.490      |                                    (e)             |
|POLY 1.5           |                                           P=0.494      |                                    (e)             |
|POLY 6             |                                           P=0.483      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.478      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.500      |                                    (e)             |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 6
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  3/50 (6%)                5/50 (10%)   |           26/50 (52%)              27/50 (54%)     |
|POLY-3 ADJUSTED (b)|                  6.9%                     12.0%        |           56.7%                    56.6%           |
|TERMINAL (d)       |                  3/30 (10%)               4/22 (18%)   |           21/35 (60%)              22/40 (55%)     |
|FIRST INCIDENCE    |                  726 (T)                  695          |           609                      687             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.207      |                                    P=0.406N        |
|POLY 3             |                                           P=0.336      |                                    P=0.576N        |
|POLY 1.5           |                                           P=0.345      |                                    P=0.531         |
|POLY 6             |                                           P=0.323      |                                    P=0.496N        |
|LOGISTIC REGRESSION|                                           P=0.246      |                                    P=0.461N        |
|COCH-ARM / FISHERS |                                           P=0.357      |                                    P=0.500         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  4/50 (8%)                5/50 (10%)   |           26/50 (52%)              27/50 (54%)     |
|POLY-3 ADJUSTED (b)|                  9.2%                     12.0%        |           56.7%                    56.6%           |
|TERMINAL (d)       |                  3/30 (10%)               4/22 (18%)   |           21/35 (60%)              22/40 (55%)     |
|FIRST INCIDENCE    |                  688                      695          |           609                      687             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.333      |                                    P=0.406N        |
|POLY 3             |                                           P=0.476      |                                    P=0.576N        |
|POLY 1.5           |                                           P=0.486      |                                    P=0.531         |
|POLY 6             |                                           P=0.459      |                                    P=0.496N        |
|LOGISTIC REGRESSION|                                           P=0.401      |                                    P=0.461N        |
|COCH-ARM / FISHERS |                                           P=0.500      |                                    P=0.500         |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 7
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  4/50 (8%)                7/50 (14%)   |           26/50 (52%)              27/50 (54%)     |
|POLY-3 ADJUSTED (b)|                  9.2%                     16.7%        |           56.7%                    56.6%           |
|TERMINAL (d)       |                  3/30 (10%)               5/22 (23%)   |           21/35 (60%)              22/40 (55%)     |
|FIRST INCIDENCE    |                  688                      695          |           609                      687             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.133      |                                    P=0.406N        |
|POLY 3             |                                           P=0.238      |                                    P=0.576N        |
|POLY 1.5           |                                           P=0.248      |                                    P=0.531         |
|POLY 6             |                                           P=0.222      |                                    P=0.496N        |
|LOGISTIC REGRESSION|                                           P=0.180      |                                    P=0.461N        |
|COCH-ARM / FISHERS |                                           P=0.262      |                                    P=0.500         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Parathyroid Gland                                                                                                                |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/48 (0%)                0/45 (0%)    |           2/43 (5%)                0/43 (0%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     0.0%         |           5.2%                     0.0%            |
|TERMINAL (d)       |                  0/29 (0%)                0/19 (0%)    |           2/29 (7%)                0/35 (0%)       |
|FIRST INCIDENCE    |                  ---                      ---          |           732 (T)                  ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           (e)          |                                    P=0.198N        |
|POLY 3             |                                           (e)          |                                    P=0.219N        |
|POLY 1.5           |                                           (e)          |                                    P=0.230N        |
|POLY 6             |                                           (e)          |                                    P=0.205N        |
|LOGISTIC REGRESSION|                                           (e)          |                                    (e)             |
|COCH-ARM / FISHERS |                                           (e)          |                                    P=0.247N        |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 8
                     Statistical Analysis of Primary Tumors 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 or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  8/50 (16%)               9/50 (18%)   |           12/50 (24%)              17/50 (34%)     |
|POLY-3 ADJUSTED (b)|                  18.4%                    21.3%        |           26.2%                    35.8%           |
|TERMINAL (d)       |                  7/30 (23%)               5/22 (23%)   |           8/35 (23%)               14/40 (35%)     |
|FIRST INCIDENCE    |                  688                      660          |           609                      677             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.278      |                                    P=0.317         |
|POLY 3             |                                           P=0.473      |                                    P=0.218         |
|POLY 1.5           |                                           P=0.484      |                                    P=0.197         |
|POLY 6             |                                           P=0.457      |                                    P=0.248         |
|LOGISTIC REGRESSION|                                           P=0.392      |                                    P=0.245         |
|COCH-ARM / FISHERS |                                           P=0.500      |                                    P=0.189         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  8/50 (16%)               9/50 (18%)   |           12/50 (24%)              17/50 (34%)     |
|POLY-3 ADJUSTED (b)|                  18.4%                    21.3%        |           26.2%                    35.8%           |
|TERMINAL (d)       |                  7/30 (23%)               5/22 (23%)   |           8/35 (23%)               14/40 (35%)     |
|FIRST INCIDENCE    |                  688                      660          |           609                      677             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.278      |                                    P=0.317         |
|POLY 3             |                                           P=0.473      |                                    P=0.218         |
|POLY 1.5           |                                           P=0.484      |                                    P=0.197         |
|POLY 6             |                                           P=0.457      |                                    P=0.248         |
|LOGISTIC REGRESSION|                                           P=0.392      |                                    P=0.245         |
|COCH-ARM / FISHERS |                                           P=0.500      |                                    P=0.189         |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 9
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor                                                                       |
|     (M or B), Basal Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepitheliom                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  7/50 (14%)               4/50 (8%)    |           0/50 (0%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  15.8%                    9.5%         |           0.0%                     2.1%            |
|TERMINAL (d)       |                  5/30 (17%)               2/22 (9%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  505                      617          |           ---                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.394N     |                                    P=0.527         |
|POLY 3             |                                           P=0.293N     |                                    P=0.500         |
|POLY 1.5           |                                           P=0.280N     |                                    P=0.500         |
|POLY 6             |                                           P=0.312N     |                                    P=0.501         |
|LOGISTIC REGRESSION|                                           P=0.263N     |                                    P=0.527         |
|COCH-ARM / FISHERS |                                           P=0.262N     |                                    P=0.500         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma or Fibrosarcoma                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  3/50 (6%)                1/50 (2%)    |           0/50 (0%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  6.8%                     2.4%         |           0.0%                     2.1%            |
|TERMINAL (d)       |                  2/30 (7%)                1/22 (5%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  610                      726 (T)      |           ---                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.389N     |                                    P=0.527         |
|POLY 3             |                                           P=0.329N     |                                    P=0.500         |
|POLY 1.5           |                                           P=0.319N     |                                    P=0.500         |
|POLY 6             |                                           P=0.346N     |                                    P=0.501         |
|LOGISTIC REGRESSION|                                           P=0.319N     |                                    P=0.527         |
|COCH-ARM / FISHERS |                                           P=0.309N     |                                    P=0.500         |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 10
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma,                                                                        |
|     or Fibrous Histiocytoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  4/50 (8%)                4/50 (8%)    |           0/50 (0%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  9.1%                     9.4%         |           0.0%                     2.1%            |
|TERMINAL (d)       |                  2/30 (7%)                1/22 (5%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  610                      365          |           ---                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.542      |                                    P=0.527         |
|POLY 3             |                                           P=0.628      |                                    P=0.500         |
|POLY 1.5           |                                           P=0.635      |                                    P=0.500         |
|POLY 6             |                                           P=0.613      |                                    P=0.501         |
|LOGISTIC REGRESSION|                                           P=0.609N     |                                    P=0.527         |
|COCH-ARM / FISHERS |                                           P=0.643N     |                                    P=0.500         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                0/50 (0%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  4.6%                     0.0%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  2/30 (7%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  726 (T)                  ---          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.308N     |                                    (e)             |
|POLY 3             |                                           P=0.252N     |                                    (e)             |
|POLY 1.5           |                                           P=0.246N     |                                    (e)             |
|POLY 6             |                                           P=0.262N     |                                    (e)             |
|LOGISTIC REGRESSION|                                           (e)          |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.247N     |                                    (e)             |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 11
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  3/50 (6%)                2/50 (4%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  6.9%                     4.7%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  2/30 (7%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  674                      365          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.577N     |                                    (e)             |
|POLY 3             |                                           P=0.513N     |                                    (e)             |
|POLY 1.5           |                                           P=0.506N     |                                    (e)             |
|POLY 6             |                                           P=0.527N     |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.447N     |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  5/50 (10%)               3/50 (6%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  11.3%                    7.1%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  3/30 (10%)               1/22 (5%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  505                      617          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.455N     |                                    (e)             |
|POLY 3             |                                           P=0.388N     |                                    (e)             |
|POLY 1.5           |                                           P=0.375N     |                                    (e)             |
|POLY 6             |                                           P=0.408N     |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.336N     |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.357N     |                                    (e)             |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 12
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Lipoma                                                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  0/50 (0%)                0/50 (0%)    |           2/50 (4%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  0.0%                     0.0%         |           4.4%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                0/22 (0%)    |           1/35 (3%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  ---                      ---          |           588                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           (e)          |                                    P=0.225N        |
|POLY 3             |                                           (e)          |                                    P=0.227N        |
|POLY 1.5           |                                           (e)          |                                    P=0.234N        |
|POLY 6             |                                           (e)          |                                    P=0.218N        |
|LOGISTIC REGRESSION|                                           (e)          |                                    P=0.222N        |
|COCH-ARM / FISHERS |                                           (e)          |                                    P=0.247N        |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Schwannoma Malignant                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR 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    |                  ---                      628          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.242      |                                    (e)             |
|POLY 3             |                                           P=0.234      |                                    (e)             |
|POLY 1.5           |                                           P=0.235      |                                    (e)             |
|POLY 6             |                                           P=0.232      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.265      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.247      |                                    (e)             |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 13
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, Squamous Cell                                                                           |
|     Carcinoma or Keratoacanthoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  6/50 (12%)               3/50 (6%)    |           0/50 (0%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  13.5%                    7.1%         |           0.0%                     2.1%            |
|TERMINAL (d)       |                  4/30 (13%)               1/22 (5%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  505                      617          |           ---                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.345N     |                                    P=0.527         |
|POLY 3             |                                           P=0.270N     |                                    P=0.500         |
|POLY 1.5           |                                           P=0.259N     |                                    P=0.500         |
|POLY 6             |                                           P=0.287N     |                                    P=0.501         |
|LOGISTIC REGRESSION|                                           P=0.232N     |                                    P=0.527         |
|COCH-ARM / FISHERS |                                           P=0.243N     |                                    P=0.500         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, or Keratoacanthoma                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  6/50 (12%)               3/50 (6%)    |           0/50 (0%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  13.5%                    7.1%         |           0.0%                     2.1%            |
|TERMINAL (d)       |                  4/30 (13%)               1/22 (5%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  505                      617          |           ---                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.345N     |                                    P=0.527         |
|POLY 3             |                                           P=0.270N     |                                    P=0.500         |
|POLY 1.5           |                                           P=0.259N     |                                    P=0.500         |
|POLY 6             |                                           P=0.287N     |                                    P=0.501         |
|LOGISTIC REGRESSION|                                           P=0.232N     |                                    P=0.527         |
|COCH-ARM / FISHERS |                                           P=0.243N     |                                    P=0.500         |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 14
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  49/50 (98%)              47/50 (94%)  |                                                    |
|POLY-3 ADJUSTED (b)|                  99.5%                    98.5%        |                                                    |
|TERMINAL (d)       |                  30/30 (100%)             22/22 (100%) |                                                    |
|FIRST INCIDENCE    |                  505                      532          |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.153      |                                                    |
|POLY 3             |                                           P=0.857N     |                                                    |
|POLY 1.5           |                                           P=0.522N     |                                                    |
|POLY 6             |                                           P=1.000N     |                                                    |
|LOGISTIC REGRESSION|                                           P=0.469N     |                                                    |
|COCH-ARM / FISHERS |                                           P=0.309N     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  7/50 (14%)               5/50 (10%)   |           8/50 (16%)               13/50 (26%)     |
|POLY-3 ADJUSTED (b)|                  16.1%                    11.9%        |           17.7%                    27.6%           |
|TERMINAL (d)       |                  7/30 (23%)               3/22 (14%)   |           7/35 (20%)               13/40 (33%)     |
|FIRST INCIDENCE    |                  726 (T)                  623          |           719                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.573N     |                                    P=0.252         |
|POLY 3             |                                           P=0.402N     |                                    P=0.185         |
|POLY 1.5           |                                           P=0.393N     |                                    P=0.170         |
|POLY 6             |                                           P=0.416N     |                                    P=0.207         |
|LOGISTIC REGRESSION|                                           P=0.467N     |                                    P=0.230         |
|COCH-ARM / FISHERS |                                           P=0.380N     |                                    P=0.163         |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 15
                     Statistical Analysis of Primary Tumors 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                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                2/50 (4%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  4.6%                     4.8%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  2/30 (7%)                1/22 (5%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  726 (T)                  688          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.596      |                                    (e)             |
|POLY 3             |                                           P=0.684      |                                    (e)             |
|POLY 1.5           |                                           P=0.688      |                                    (e)             |
|POLY 6             |                                           P=0.678      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.646      |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.691N     |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  9/50 (18%)               7/50 (14%)   |           8/50 (16%)               13/50 (26%)     |
|POLY-3 ADJUSTED (b)|                  20.7%                    16.6%        |           17.7%                    27.6%           |
|TERMINAL (d)       |                  9/30 (30%)               4/22 (18%)   |           7/35 (20%)               13/40 (33%)     |
|FIRST INCIDENCE    |                  726 (T)                  623          |           719                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.599      |                                    P=0.252         |
|POLY 3             |                                           P=0.416N     |                                    P=0.185         |
|POLY 1.5           |                                           P=0.407N     |                                    P=0.170         |
|POLY 6             |                                           P=0.429N     |                                    P=0.207         |
|LOGISTIC REGRESSION|                                           P=0.500N     |                                    P=0.230         |
|COCH-ARM / FISHERS |                                           P=0.393N     |                                    P=0.163         |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 16
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  3/50 (6%)                0/50 (0%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  6.8%                     0.0%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  1/30 (3%)                0/22 (0%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  450                      ---          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.165N     |                                    (e)             |
|POLY 3             |                                           P=0.134N     |                                    (e)             |
|POLY 1.5           |                                           P=0.128N     |                                    (e)             |
|POLY 6             |                                           P=0.144N     |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.093N     |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.121N     |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  4/50 (8%)                0/50 (0%)    |           0/50 (0%)                1/50 (2%)       |
|POLY-3 ADJUSTED (b)|                  9.0%                     0.0%         |           0.0%                     2.1%            |
|TERMINAL (d)       |                  1/30 (3%)                0/22 (0%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  450                      ---          |           ---                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.087N     |                                    P=0.527         |
|POLY 3             |                                           P=0.072N     |                                    P=0.500         |
|POLY 1.5           |                                           P=0.067N     |                                    P=0.500         |
|POLY 6             |                                           P=0.080N     |                                    P=0.501         |
|LOGISTIC REGRESSION|                                           P=0.042N*    |                                    P=0.527         |
|COCH-ARM / FISHERS |                                           P=0.059N     |                                    P=0.500         |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 17
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |           14/50 (28%)              5/50 (10%)      |
|POLY-3 ADJUSTED (b)|                                                        |           30.5%                    10.6%           |
|TERMINAL (d)       |                                                        |           12/35 (34%)              5/40 (13%)      |
|FIRST INCIDENCE    |                                                        |           508                      732 (T)         |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |                                    P=0.010N*       |
|POLY 3             |                                                        |                                    P=0.015N*       |
|POLY 1.5           |                                                        |                                    P=0.017N*       |
|POLY 6             |                                                        |                                    P=0.012N*       |
|LOGISTIC REGRESSION|                                                        |                                    P=0.015N*       |
|COCH-ARM / FISHERS |                                                        |                                    P=0.020N*       |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/50 (2%)                0/50 (0%)    |           0/50 (0%)                2/50 (4%)       |
|POLY-3 ADJUSTED (b)|                  2.3%                     0.0%         |           0.0%                     4.2%            |
|TERMINAL (d)       |                  1/30 (3%)                0/22 (0%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  726 (T)                  ---          |           ---                      687             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.562N     |                                    P=0.273         |
|POLY 3             |                                           P=0.518N     |                                    P=0.243         |
|POLY 1.5           |                                           P=0.510N     |                                    P=0.239         |
|POLY 6             |                                           P=0.530N     |                                    P=0.247         |
|LOGISTIC REGRESSION|                                           (e)          |                                    P=0.238         |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    P=0.247         |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 18
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  1/50 (2%)                0/50 (0%)    |           0/50 (0%)                2/50 (4%)       |
|POLY-3 ADJUSTED (b)|                  2.3%                     0.0%         |           0.0%                     4.2%            |
|TERMINAL (d)       |                  1/30 (3%)                0/22 (0%)    |           0/35 (0%)                1/40 (3%)       |
|FIRST INCIDENCE    |                  726 (T)                  ---          |           ---                      687             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.562N     |                                    P=0.273         |
|POLY 3             |                                           P=0.518N     |                                    P=0.243         |
|POLY 1.5           |                                           P=0.510N     |                                    P=0.239         |
|POLY 6             |                                           P=0.530N     |                                    P=0.247         |
|LOGISTIC REGRESSION|                                           (e)          |                                    P=0.238         |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    P=0.247         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear, or                                                                           |
|     Undifferentiated                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  33/50 (66%)              35/50 (70%)  |           14/50 (28%)              10/50 (20%)     |
|POLY-3 ADJUSTED (b)|                  68.0%                    75.3%        |           28.8%                    21.1%           |
|TERMINAL (d)       |                  16/30 (53%)              15/22 (68%)  |           5/35 (14%)               9/40 (23%)      |
|FIRST INCIDENCE    |                  450                      446          |           508                      652             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.143      |                                    P=0.175N        |
|POLY 3             |                                           P=0.282      |                                    P=0.264N        |
|POLY 1.5           |                                           P=0.332      |                                    P=0.262N        |
|POLY 6             |                                           P=0.227      |                                    P=0.266N        |
|LOGISTIC REGRESSION|                                           P=0.396      |                                    P=0.243N        |
|COCH-ARM / FISHERS |                                           P=0.415      |                                    P=0.241N        |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 19
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma: Benign, Malignant, NOS                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                2/50 (4%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  4.6%                     4.8%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                1/22 (5%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  610                      663          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.631      |                                    (e)             |
|POLY 3             |                                           P=0.682      |                                    (e)             |
|POLY 1.5           |                                           P=0.687      |                                    (e)             |
|POLY 6             |                                           P=0.673      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.693N     |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.691N     |                                    (e)             |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma: Malignant                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  2/50 (4%)                2/50 (4%)    |           0/50 (0%)                0/50 (0%)       |
|POLY-3 ADJUSTED (b)|                  4.6%                     4.8%         |           0.0%                     0.0%            |
|TERMINAL (d)       |                  0/30 (0%)                1/22 (5%)    |           0/35 (0%)                0/40 (0%)       |
|FIRST INCIDENCE    |                  610                      663          |           ---                      ---             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.631      |                                    (e)             |
|POLY 3             |                                           P=0.682      |                                    (e)             |
|POLY 1.5           |                                           P=0.687      |                                    (e)             |
|POLY 6             |                                           P=0.673      |                                    (e)             |
|LOGISTIC REGRESSION|                                           P=0.693N     |                                    (e)             |
|COCH-ARM / FISHERS |                                           P=0.691N     |                                    (e)             |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 20
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  50/50 (100%)             47/50 (94%)  |           37/50 (74%)              41/50 (82%)     |
|POLY-3 ADJUSTED (b)|                  100.0%                   98.5%        |           78.8%                    85.4%           |
|TERMINAL (d)       |                  30/30 (100%)             22/22 (100%) |           30/35 (86%)              34/40 (85%)     |
|FIRST INCIDENCE    |                  450                      532          |           508                      677             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.193      |                                    P=0.519N        |
|POLY 3             |                                           P=0.758N     |                                    P=0.272         |
|POLY 1.5           |                                           P=0.303N     |                                    P=0.221         |
|POLY 6             |                                           P=1.000N     |                                    P=0.380         |
|LOGISTIC REGRESSION|                                           P=0.165N     |                                    P=0.422         |
|COCH-ARM / FISHERS |                                           P=0.121N     |                                    P=0.235         |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  35/50 (70%)              41/50 (82%)  |           15/50 (30%)              15/50 (30%)     |
|POLY-3 ADJUSTED (b)|                  71.5%                    83.6%        |           30.6%                    31.1%           |
|TERMINAL (d)       |                  17/30 (57%)              15/22 (68%)  |           5/35 (14%)               12/40 (30%)     |
|FIRST INCIDENCE    |                  450                      365          |           508                      491             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.059      |                                    P=0.452N        |
|POLY 3             |                                           P=0.112      |                                    P=0.568         |
|POLY 1.5           |                                           P=0.115      |                                    P=0.566         |
|POLY 6             |                                           P=0.110      |                                    P=0.567         |
|LOGISTIC REGRESSION|                                           P=0.146      |                                    P=0.557         |
|COCH-ARM / FISHERS |                                           P=0.121      |                                    P=0.586N        |
|=================================================================================================================================|
       Date:  06/01/00                           EXPERIMENT: 56348 TEST: 03                                            Page 21
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                       CITRAL
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |                  UNTREAT                  VEHICLE      |           UNTREAT                  VEHICLE         |
|                   |                  CONTROL                  CONTROL      |           CONTROL                  CONTROL         |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                  #                        #            |           #                        #               |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                  50/50 (100%)             49/50 (98%)  |           47/50 (94%)              45/50 (90%)     |
|POLY-3 ADJUSTED (b)|                  100.0%                   99.3%        |           94.0%                    91.8%           |
|TERMINAL (d)       |                  30/30 (100%)             22/22 (100%) |           32/35 (91%)              36/40 (90%)     |
|FIRST INCIDENCE    |                  450                      365          |           508                      491             |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                           P=0.126      |                                    P=0.120N        |
|POLY 3             |                                           P=0.971N     |                                    P=0.491N        |
|POLY 1.5           |                                           P=0.759N     |                                    P=0.487N        |
|POLY 6             |                                           P=1.000N     |                                    P=0.491N        |
|LOGISTIC REGRESSION|                                           P=0.636N     |                                    P=0.383N        |
|COCH-ARM / FISHERS |                                           P=0.500N     |                                    P=0.357N        |
|=================================================================================================================================|
(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).