https://ntp.niehs.nih.gov/go/5310

TDMS Study 96007-03 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08
LAB: Battelle Columbus                         TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD)                      DATE: 10/22/03
EXPERIMENT: 96007 TEST: 03                                                                                     TIME: 16:15:51
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE
CONT: NO1-ES-75411                              ROUTE: GAVAGE                                                  NTP C#: 96007G
PATHOLOGIST: SELLS, DONALD                                                                                     CAS: 1746-01-6
Rats(SPRAGUE-DAWLEY)
-----------------------------
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
                                                 Heart
                                                 Islets, Pancreatic
                                                 Kidney
                                                 Liver
                                                 Lung
                                                 Ovary
                                                 Pancreas
                                                 Parathyroid Gland
                                                 Pituitary Gland
                                                 Spleen
                                                 Thymus
                                                 Thyroid Gland
                                                 Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08   
LAB: Battelle Columbus                         TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD)                      DATE: 10/22/03     
EXPERIMENT: 96007 TEST: 03                                                                                     TIME: 16:15:51     
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                      
CONT: NO1-ES-75411                              ROUTE: GAVAGE                                                  NTP C#: 96007G     
PATHOLOGIST: SELLS, DONALD                                                                                     CAS: 1746-01-6     
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF       TOXIC EQUIVALENCY FACTOR EVALUATION
===============================================================
Female Rats
------------
Organ                                  Morphology
-----                                  ----------
Adrenal Medulla                        Pheochromocytoma Benign
                                       Pheochromocytoma: Benign, Complex, Malignant, NOS
Heart                                  Schwannoma Malignant
Liver                                  Cholangiocarcinoma
                                       Hepatocellular Adenoma
                                       Hepatocellular Carcinoma, Hepatocellular Adenoma or Cholangiocarcinoma
                                       Hepatocholangioma
Lung                                   Cystic Keratinizing Epithelioma
Mammary Gland                          Fibroadenoma
                                       Fibroma, Fibroadenoma or Adenoma
                                       Fibroma, Fibroadenoma, Carcinoma, or Adenoma
Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva)
                                       Squamous Cell Carcinoma
                                       Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma
Oral Mucosa                            Squamous Cell Carcinoma
Pancreas                               Carcinoma
                                       Carcinoma or Adenoma
Pituitary Gland: Pars Distalis or Unspecified Site
                                       Adenoma
Skin                                   Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma
Thyroid Gland: C-Cell                  Adenoma
                                       Carcinoma or Adenoma
Uterus                                 Carcinoma
                                       Polyp Stromal
                                       Squamous Cell Carcinoma
All Organs                             Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated Cell Type
                                       Benign Tumors
                                       Malignant Tumors
                                       Malignant and Benign Tumors
===============================================================
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 1
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)        -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                                                                             |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              3/53 (6%)                                         1/50 (2%)                    |
|POLY-3 RATE (b)    |                              3/43.18                                           1/38.27                      |
|POLY-3 PERCENT (g) |                              7.0%                                              2.6%                         |
|TERMINAL (d)       |                              0/21 (0%)                                         0/21 (0%)                    |
|FIRST INCIDENCE    |                              642                                               702                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.305N                     |
|POLY 3             |                                                                                P=0.361N                     |
|POLY 1.5           |                                                                                P=0.355N                     |
|POLY 6             |                                                                                P=0.358N                     |
|LOGISTIC REGRESSION|                                                                                P=0.341N                     |
|COCH-ARM / FISHERS |                                                                                P=0.331N                     |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                                                                             |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              3/53 (6%)                                         2/50 (4%)                    |
|POLY-3 RATE (b)    |                              3/43.18                                           2/38.27                      |
|POLY-3 PERCENT (g) |                              7.0%                                              5.2%                         |
|TERMINAL (d)       |                              0/21 (0%)                                         1/21 (5%)                    |
|FIRST INCIDENCE    |                              642                                               702                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.497N                     |
|POLY 3             |                                                                                P=0.567N                     |
|POLY 1.5           |                                                                                P=0.559N                     |
|POLY 6             |                                                                                P=0.564N                     |
|LOGISTIC REGRESSION|                                                                                P=0.547N                     |
|COCH-ARM / FISHERS |                                                                                P=0.528N                     |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 2
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)       -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart                                                                                                                            |
|     Schwannoma Malignant                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                                                                             |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              0/52 (0%)                                         3/50 (6%)                    |
|POLY-3 RATE (b)    |                              0/41.64                                           3/38.98                      |
|POLY-3 PERCENT (g) |                              0.0%                                              7.7%                         |
|TERMINAL (d)       |                              0/21 (0%)                                         1/21 (5%)                    |
|FIRST INCIDENCE    |                              ---                                               484                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.121                      |
|POLY 3             |                                                                                P=0.110                      |
|POLY 1.5           |                                                                                P=0.110                      |
|POLY 6             |                                                                                P=0.112                      |
|LOGISTIC REGRESSION|                                                                                P=0.120                      |
|COCH-ARM / FISHERS |                                                                                P=0.114                      |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Cholangiocarcinoma                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                                                                             |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              25/53 (47%)                                       2/50 (4%)                    |
|POLY-3 RATE (b)    |                              25/45.58                                          2/38.16                      |
|POLY-3 PERCENT (g) |                              54.9%                                             5.2%                         |
|TERMINAL (d)       |                              13/21 (62%)                                       1/21 (5%)                    |
|FIRST INCIDENCE    |                              610                                               729                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P<0.001N**                   |
|POLY 3             |                                                                                P<0.001N**                   |
|POLY 1.5           |                                                                                P<0.001N**                   |
|POLY 6             |                                                                                P<0.001N**                   |
|LOGISTIC REGRESSION|                                                                                P<0.001N**                   |
|COCH-ARM / FISHERS |                                                                                P<0.001N**                   |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 3
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)       -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                                                                             |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              13/53 (25%)                                       2/50 (4%)                    |
|POLY-3 RATE (b)    |                              13/43.52                                          2/38.29                      |
|POLY-3 PERCENT (g) |                              29.9%                                             5.2%                         |
|TERMINAL (d)       |                              7/21 (33%)                                        0/21 (0%)                    |
|FIRST INCIDENCE    |                              642                                               702                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.003N**                   |
|POLY 3             |                                                                                P=0.004N**                   |
|POLY 1.5           |                                                                                P=0.004N**                   |
|POLY 6             |                                                                                P=0.003N**                   |
|LOGISTIC REGRESSION|                                                                                P=0.003N**                   |
|COCH-ARM / FISHERS |                                                                                P=0.003N**                   |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma or                                                                         |
|     Cholangiocarcinoma                                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                                                                             |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              29/53 (55%)                                       4/50 (8%)                    |
|POLY-3 RATE (b)    |                              29/46.02                                          4/38.30                      |
|POLY-3 PERCENT (g) |                              63.0%                                             10.4%                        |
|TERMINAL (d)       |                              14/21 (67%)                                       1/21 (5%)                    |
|FIRST INCIDENCE    |                              610                                               702                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P<0.001N**                   |
|POLY 3             |                                                                                P<0.001N**                   |
|POLY 1.5           |                                                                                P<0.001N**                   |
|POLY 6             |                                                                                P<0.001N**                   |
|LOGISTIC REGRESSION|                                                                                P<0.001N**                   |
|COCH-ARM / FISHERS |                                                                                P<0.001N**                   |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 4
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)       -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocholangioma                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                                                                             |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              2/53 (4%)                                         0/50 (0%)                    |
|POLY-3 RATE (b)    |                              2/42.93                                           0/38.16                      |
|POLY-3 PERCENT (g) |                              4.7%                                              0.0%                         |
|TERMINAL (d)       |                              1/21 (5%)                                         0/21 (0%)                    |
|FIRST INCIDENCE    |                              638                                               ---                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.257N                     |
|POLY 3             |                                                                                P=0.279N                     |
|POLY 1.5           |                                                                                P=0.274N                     |
|POLY 6             |                                                                                P=0.275N                     |
|LOGISTIC REGRESSION|                                                                                P=0.259N                     |
|COCH-ARM / FISHERS |                                                                                P=0.262N                     |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Cystic Keratinizing Epithelioma                                                                                             |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                                                                             |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              9/52 (17%)                                        0/50 (0%)                    |
|POLY-3 RATE (b)    |                              9/42.72                                           0/38.16                      |
|POLY-3 PERCENT (g) |                              21.1%                                             0.0%                         |
|TERMINAL (d)       |                              4/21 (19%)                                        0/21 (0%)                    |
|FIRST INCIDENCE    |                              610                                               ---                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.004N**                   |
|POLY 3             |                                                                                P=0.003N**                   |
|POLY 1.5           |                                                                                P=0.003N**                   |
|POLY 6             |                                                                                P=0.003N**                   |
|LOGISTIC REGRESSION|                                                                                P=0.003N**                   |
|COCH-ARM / FISHERS |                                                                                P=0.002N**                   |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 5
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)       -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              24/53 (45%)                                       32/50 (64%)                  |
|POLY-3 RATE (b)    |                              24/47.04                                          32/44.58                     |
|POLY-3 PERCENT (g) |                              51.0%                                             71.8%                        |
|TERMINAL (d)       |                              12/21 (57%)                                       13/21 (62%)                  |
|FIRST INCIDENCE    |                              396                                               345                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.105                      |
|POLY 3             |                                                                                P=0.027 *                    |
|POLY 1.5           |                                                                                P=0.028 *                    |
|POLY 6             |                                                                                P=0.035 *                    |
|LOGISTIC REGRESSION|                                                                                P=0.034 *                    |
|COCH-ARM / FISHERS |                                                                                P=0.044 *                    |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              24/53 (45%)                                       32/50 (64%)                  |
|POLY-3 RATE (b)    |                              24/47.04                                          32/44.58                     |
|POLY-3 PERCENT (g) |                              51.0%                                             71.8%                        |
|TERMINAL (d)       |                              12/21 (57%)                                       13/21 (62%)                  |
|FIRST INCIDENCE    |                              396                                               345                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.105                      |
|POLY 3             |                                                                                P=0.027 *                    |
|POLY 1.5           |                                                                                P=0.028 *                    |
|POLY 6             |                                                                                P=0.035 *                    |
|LOGISTIC REGRESSION|                                                                                P=0.034 *                    |
|COCH-ARM / FISHERS |                                                                                P=0.044 *                    |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 6
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)       -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              24/53 (45%)                                       33/50 (66%)                  |
|POLY-3 RATE (b)    |                              24/47.04                                          33/45.18                     |
|POLY-3 PERCENT (g) |                              51.0%                                             73.0%                        |
|TERMINAL (d)       |                              12/21 (57%)                                       13/21 (62%)                  |
|FIRST INCIDENCE    |                              396                                               345                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.080                      |
|POLY 3             |                                                                                P=0.019 *                    |
|POLY 1.5           |                                                                                P=0.018 *                    |
|POLY 6             |                                                                                P=0.027 *                    |
|LOGISTIC REGRESSION|                                                                                P=0.022 *                    |
|COCH-ARM / FISHERS |                                                                                P=0.027 *                    |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva)                                                                       |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              10/53 (19%)                                       5/50 (10%)                   |
|POLY-3 RATE (b)    |                              10/45.45                                          5/40.28                      |
|POLY-3 PERCENT (g) |                              22.0%                                             12.4%                        |
|TERMINAL (d)       |                              2/21 (10%)                                        0/21 (0%)                    |
|FIRST INCIDENCE    |                              546                                               520                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.202N                     |
|POLY 3             |                                                                                P=0.193N                     |
|POLY 1.5           |                                                                                P=0.186N                     |
|POLY 6             |                                                                                P=0.189N                     |
|LOGISTIC REGRESSION|                                                                                P=0.115N                     |
|COCH-ARM / FISHERS |                                                                                P=0.160N                     |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 7
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)       -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva)                                                                       |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              10/53 (19%)                                       5/50 (10%)                   |
|POLY-3 RATE (b)    |                              10/45.45                                          5/40.28                      |
|POLY-3 PERCENT (g) |                              22.0%                                             12.4%                        |
|TERMINAL (d)       |                              2/21 (10%)                                        0/21 (0%)                    |
|FIRST INCIDENCE    |                              546                                               520                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.202N                     |
|POLY 3             |                                                                                P=0.193N                     |
|POLY 1.5           |                                                                                P=0.186N                     |
|POLY 6             |                                                                                P=0.189N                     |
|LOGISTIC REGRESSION|                                                                                P=0.115N                     |
|COCH-ARM / FISHERS |                                                                                P=0.160N                     |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Mucosa                                                                                                                      |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              10/53 (19%)                                       5/50 (10%)                   |
|POLY-3 RATE (b)    |                              10/45.45                                          5/40.28                      |
|POLY-3 PERCENT (g) |                              22.0%                                             12.4%                        |
|TERMINAL (d)       |                              2/21 (10%)                                        0/21 (0%)                    |
|FIRST INCIDENCE    |                              546                                               520                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.202N                     |
|POLY 3             |                                                                                P=0.193N                     |
|POLY 1.5           |                                                                                P=0.186N                     |
|POLY 6             |                                                                                P=0.189N                     |
|LOGISTIC REGRESSION|                                                                                P=0.115N                     |
|COCH-ARM / FISHERS |                                                                                P=0.160N                     |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 8
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)       -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                                                                             |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              2/51 (4%)                                         1/49 (2%)                    |
|POLY-3 RATE (b)    |                              2/41.18                                           1/37.76                      |
|POLY-3 PERCENT (g) |                              4.9%                                              2.7%                         |
|TERMINAL (d)       |                              1/21 (5%)                                         1/21 (5%)                    |
|FIRST INCIDENCE    |                              641                                               731 (T)                      |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.513N                     |
|POLY 3             |                                                                                P=0.541N                     |
|POLY 1.5           |                                                                                P=0.538N                     |
|POLY 6             |                                                                                P=0.534N                     |
|LOGISTIC REGRESSION|                                                                                P=0.522N                     |
|COCH-ARM / FISHERS |                                                                                P=0.515N                     |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                                                                             |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              3/51 (6%)                                         1/49 (2%)                    |
|POLY-3 RATE (b)    |                              3/41.18                                           1/37.76                      |
|POLY-3 PERCENT (g) |                              7.3%                                              2.7%                         |
|TERMINAL (d)       |                              2/21 (10%)                                        1/21 (5%)                    |
|FIRST INCIDENCE    |                              641                                               731 (T)                      |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.315N                     |
|POLY 3             |                                                                                P=0.345N                     |
|POLY 1.5           |                                                                                P=0.342N                     |
|POLY 6             |                                                                                P=0.337N                     |
|LOGISTIC REGRESSION|                                                                                P=0.320N                     |
|COCH-ARM / FISHERS |                                                                                P=0.324N                     |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 9
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)       -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                                                                             |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              11/52 (21%)                                       19/50 (38%)                  |
|POLY-3 RATE (b)    |                              11/44.01                                          19/39.99                     |
|POLY-3 PERCENT (g) |                              25.0%                                             47.5%                        |
|TERMINAL (d)       |                              4/21 (19%)                                        9/21 (43%)                   |
|FIRST INCIDENCE    |                              604                                               584                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.081                      |
|POLY 3             |                                                                                P=0.023 *                    |
|POLY 1.5           |                                                                                P=0.028 *                    |
|POLY 6             |                                                                                P=0.023 *                    |
|LOGISTIC REGRESSION|                                                                                P=0.027 *                    |
|COCH-ARM / FISHERS |                                                                                P=0.049 *                    |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma,                                                                        |
|     or Fibrous Histiocytoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              1/53 (2%)                                         2/50 (4%)                    |
|POLY-3 RATE (b)    |                              1/42.65                                           2/39.00                      |
|POLY-3 PERCENT (g) |                              2.3%                                              5.1%                         |
|TERMINAL (d)       |                              0/21 (0%)                                         1/21 (5%)                    |
|FIRST INCIDENCE    |                              717                                               394                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.493                      |
|POLY 3             |                                                                                P=0.479                      |
|POLY 1.5           |                                                                                P=0.480                      |
|POLY 6             |                                                                                P=0.484                      |
|LOGISTIC REGRESSION|                                                                                P=0.533                      |
|COCH-ARM / FISHERS |                                                                                P=0.478                      |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 10
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)       -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                                                                             |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              11/52 (21%)                                       13/49 (27%)                  |
|POLY-3 RATE (b)    |                              11/43.05                                          13/38.54                     |
|POLY-3 PERCENT (g) |                              25.6%                                             33.7%                        |
|TERMINAL (d)       |                              6/21 (29%)                                        7/21 (33%)                   |
|FIRST INCIDENCE    |                              638                                               584                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.401                      |
|POLY 3             |                                                                                P=0.288                      |
|POLY 1.5           |                                                                                P=0.300                      |
|POLY 6             |                                                                                P=0.295                      |
|LOGISTIC REGRESSION|                                                                                P=0.307                      |
|COCH-ARM / FISHERS |                                                                                P=0.344                      |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                                                                             |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              11/52 (21%)                                       14/49 (29%)                  |
|POLY-3 RATE (b)    |                              11/43.05                                          14/38.54                     |
|POLY-3 PERCENT (g) |                              25.6%                                             36.3%                        |
|TERMINAL (d)       |                              6/21 (29%)                                        8/21 (38%)                   |
|FIRST INCIDENCE    |                              638                                               584                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.319                      |
|POLY 3             |                                                                                P=0.208                      |
|POLY 1.5           |                                                                                P=0.221                      |
|POLY 6             |                                                                                P=0.211                      |
|LOGISTIC REGRESSION|                                                                                P=0.228                      |
|COCH-ARM / FISHERS |                                                                                P=0.264                      |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 11
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)       -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              1/53 (2%)                                         2/50 (4%)                    |
|POLY-3 RATE (b)    |                              1/42.66                                           2/38.16                      |
|POLY-3 PERCENT (g) |                              2.3%                                              5.2%                         |
|TERMINAL (d)       |                              0/21 (0%)                                         2/21 (10%)                   |
|FIRST INCIDENCE    |                              716                                               731 (T)                      |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.500                      |
|POLY 3             |                                                                                P=0.475                      |
|POLY 1.5           |                                                                                P=0.477                      |
|POLY 6             |                                                                                P=0.477                      |
|LOGISTIC REGRESSION|                                                                                P=0.501                      |
|COCH-ARM / FISHERS |                                                                                P=0.478                      |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              8/53 (15%)                                        4/50 (8%)                    |
|POLY-3 RATE (b)    |                              8/44.05                                           4/38.16                      |
|POLY-3 PERCENT (g) |                              18.2%                                             10.5%                        |
|TERMINAL (d)       |                              3/21 (14%)                                        3/21 (14%)                   |
|FIRST INCIDENCE    |                              598                                               729                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.206N                     |
|POLY 3             |                                                                                P=0.259N                     |
|POLY 1.5           |                                                                                P=0.245N                     |
|POLY 6             |                                                                                P=0.266N                     |
|LOGISTIC REGRESSION|                                                                                P=0.229N                     |
|COCH-ARM / FISHERS |                                                                                P=0.209N                     |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 12
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)       -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              0/53 (0%)                                         2/50 (4%)                    |
|POLY-3 RATE (b)    |                              0/42.60                                           2/38.16                      |
|POLY-3 PERCENT (g) |                              0.0%                                              5.2%                         |
|TERMINAL (d)       |                              0/21 (0%)                                         2/21 (10%)                   |
|FIRST INCIDENCE    |                              ---                                               731 (T)                      |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.237                      |
|POLY 3             |                                                                                P=0.225                      |
|POLY 1.5           |                                                                                P=0.226                      |
|POLY 6             |                                                                                P=0.226                      |
|LOGISTIC REGRESSION|                                                                                P=0.237                      |
|COCH-ARM / FISHERS |                                                                                P=0.233                      |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              2/53 (4%)                                         1/50 (2%)                    |
|POLY-3 RATE (b)    |                              2/42.60                                           1/39.05                      |
|POLY-3 PERCENT (g) |                              4.7%                                              2.6%                         |
|TERMINAL (d)       |                              2/21 (10%)                                        0/21 (0%)                    |
|FIRST INCIDENCE    |                              731 (T)                                           345                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.509N                     |
|POLY 3             |                                                                                P=0.541N                     |
|POLY 1.5           |                                                                                P=0.540N                     |
|POLY 6             |                                                                                P=0.531N                     |
|LOGISTIC REGRESSION|                                                                                P=0.451N                     |
|COCH-ARM / FISHERS |                                                                                P=0.522N                     |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 13
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)       -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              42/53 (79%)                                       41/50 (82%)                  |
|POLY-3 RATE (b)    |                              42/49.59                                          41/45.87                     |
|POLY-3 PERCENT (g) |                              84.7%                                             89.4%                        |
|TERMINAL (d)       |                              18/21 (86%)                                       18/21 (86%)                  |
|FIRST INCIDENCE    |                              396                                               345                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.526                      |
|POLY 3             |                                                                                P=0.343                      |
|POLY 1.5           |                                                                                P=0.356                      |
|POLY 6             |                                                                                P=0.388                      |
|LOGISTIC REGRESSION|                                                                                P=0.274                      |
|COCH-ARM / FISHERS |                                                                                P=0.459                      |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              34/53 (64%)                                       19/50 (38%)                  |
|POLY-3 RATE (b)    |                              34/48.63                                          19/42.85                     |
|POLY-3 PERCENT (g) |                              69.9%                                             44.3%                        |
|TERMINAL (d)       |                              14/21 (67%)                                       9/21 (43%)                   |
|FIRST INCIDENCE    |                              546                                               345                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.023N*                    |
|POLY 3             |                                                                                P=0.008N**                   |
|POLY 1.5           |                                                                                P=0.007N**                   |
|POLY 6             |                                                                                P=0.010N*                    |
|LOGISTIC REGRESSION|                                                                                P=0.008N**                   |
|COCH-ARM / FISHERS |                                                                                P=0.007N**                   |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
       Date:  10/22/03                           EXPERIMENT: 96007 TEST: 03                                            Page 14
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY)       -        TOXIC EQUIVALENCY FACTOR EVALUATION
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                                                                             |
|                   |                                                      Females                                                |
|Dose               |                              100                                               100 NG/                      |
|                   |                              NG/KG                                             KG/STOP                      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                              #                                                 #                            |
|-----------        |                                                                                                             |
|OVERALL (a)        |                              50/53 (94%)                                       46/50 (92%)                  |
|POLY-3 RATE (b)    |                              50/51.78                                          46/48.66                     |
|POLY-3 PERCENT (g) |                              96.6%                                             94.5%                        |
|TERMINAL (d)       |                              20/21 (95%)                                       19/21 (91%)                  |
|FIRST INCIDENCE    |                              396                                               345                          |
|-------------------|                                                                                                             |
|STATISTICAL TESTS  |                                                                                                             |
|-------------------|                                                                                                             |
|LIFE TABLE         |                                                                                P=0.458N                     |
|POLY 3             |                                                                                P=0.501N                     |
|POLY 1.5           |                                                                                P=0.526N                     |
|POLY 6             |                                                                                P=0.464N                     |
|LOGISTIC REGRESSION|                                                                                P=0.613N                     |
|COCH-ARM / FISHERS |                                                                                P=0.467N                     |
|ORDER RESTRICTED   |                                                                                (e)                          |
|=================================================================================================================================|
(a)  Number of tumor-bearing animals /  number of animals examined at site.
(b)  Number of tumor-bearing animals / Poly-3 number 
(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.
(g)  Poly-3 adjusted lifetime tumor incidence.
(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).