TDMS Study 96007-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 11/25/02
EXPERIMENT: 96007 TEST: 03 TIME: 12:01:19
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1
CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007G
PATHOLOGIST: SELLS, DONALD CAS: 1746-01-6
------------------------------------------------------------------------------------------------------------------------------------
31 WEEK SSAC
REASONS FOR REMOVAL: 25017 Scheduled Sacrifice
REMOVAL DATE RANGE: 123098 123198
TREATMENT GROUPS: INCLUDE 001 0 NG/KG
INCLUDE 002 3 NG/KG
INCLUDE 003 10 NG/KG
INCLUDE 004 22 NG/KG
INCLUDE 005 46 NG/KG
INCLUDE 006 100 NG/KG
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 11/25/02
EXPERIMENT: 96007 TEST: 03 TIME: 12:01:19
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 Cortex Hypertrophy
Liver Fatty Change Diffuse
Mixed Cell Focus
Pigmentation
Toxic Hepatopathy
Liver: Hepatocyte Hypertrophy
Multinucleated
Pancreas: Acinus Vacuolization Cytoplasmic
Thymus Atrophy
Thyroid Gland: Follicular Cell Hypertrophy
Uterus Metaplasia
Uterus: Endometrium Hyperplasia Cystic
===============================================================
Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 1
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Hypertrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/10 (0%) 2/10 (20%) 3/10 (30%) 3/10 (30%) 3/10 (30%) 3/10 (30%) |
|POLY-3 RATE (b) | 0/0.10 2/2.08 3/3.07 3/3.07 3/3.07 3/3.07 |
|POLY-3 PERCENT (g) | 0.0% 96.3% 97.8% 97.8% 97.8% 97.8% |
|INT SACRIFICE 1 (c)| 0/10 (0%) 2/10 (20%) 3/10 (30%) 3/10 (30%) 3/10 (30%) 3/10 (30%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 213 (I) 213 (I) 213 (I) 213 (I) 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.215 P=0.234 P=0.111 P=0.111 P=0.111 P=0.111 |
|POLY 3 | P=0.173 P=0.068 P=0.025 * P=0.025 * P=0.025 * P=0.025 * |
|POLY 1.5 | P=0.177 P=0.079 P=0.030 * P=0.030 * P=0.030 * P=0.030 * |
|POLY 6 | P=0.174 P=0.067 P=0.025 * P=0.025 * P=0.025 * P=0.025 * |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.213 P=0.237 P=0.105 P=0.105 P=0.105 P=0.105 |
|ORDER RESTRICTED | P=0.064 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Fatty Change Diffuse |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 6/10 (60%) |
|POLY-3 RATE (b) | 0/0.10 0/0.10 0/0.10 0/0.10 0/0.10 6/6.04 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 99.4% |
|INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 6/10 (60%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- --- --- --- --- 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P=0.009 ** |
|POLY 3 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** |
|POLY 1.5 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** |
|POLY 6 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P=0.005 ** |
|ORDER RESTRICTED | P=0.082 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 2
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 9/10 (90%) 9/10 (90%) 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) |
|POLY-3 RATE (b) | 9/9.01 9/9.01 10/10.00 10/10.00 10/10.00 10/10.00 |
|POLY-3 PERCENT (g) | 99.9% 99.9% 100.0% 100.0% 100.0% 100.0% |
|INT SACRIFICE 1 (c)| 9/10 (90%) 9/10 (90%) 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | 213 (I) 213 (I) 213 (I) 213 (I) 213 (I) 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.267 P=0.766 P=0.500 P=0.500 P=0.500 P=0.500 |
|POLY 3 | P=0.271 P=0.741 P=0.484 P=0.484 P=0.484 P=0.484 |
|POLY 1.5 | P=0.270 P=0.741 P=0.483 P=0.483 P=0.483 P=0.483 |
|POLY 6 | P=0.274 P=0.744 P=0.489 P=0.489 P=0.489 P=0.489 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.265 P=0.763N P=0.500 P=0.500 P=0.500 P=0.500 |
|ORDER RESTRICTED | P=0.183 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Mixed Cell Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 3/10 (30%) 7/10 (70%) 4/10 (40%) 2/10 (20%) 4/10 (40%) 10/10 (100%) |
|POLY-3 RATE (b) | 3/3.07 7/7.03 4/4.06 2/2.08 4/4.06 10/10.00 |
|POLY-3 PERCENT (g) | 97.8% 99.6% 98.6% 96.3% 98.6% 100.0% |
|INT SACRIFICE 1 (c)| 3/10 (30%) 7/10 (70%) 4/10 (40%) 2/10 (20%) 4/10 (40%) 10/10 (100%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | 213 (I) 213 (I) 213 (I) 213 (I) 213 (I) 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.004 ** P=0.095 P=0.500 P=0.500N P=0.500 P=0.003 ** |
|POLY 3 | P<0.001 ** P=0.047 * P=0.385 P=0.354N P=0.385 P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.050 P=0.395 P=0.368N P=0.395 P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.047 * P=0.385 P=0.353N P=0.385 P<0.001 ** |
|LOGISTIC REGRESSION| (e) P=0.090 (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.004 ** P=0.089 P=0.500 P=0.500N P=0.500 P=0.002 ** |
|ORDER RESTRICTED | P=0.010 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 3
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Pigmentation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/10 (0%) 1/10 (10%) 8/10 (80%) 9/10 (90%) 10/10 (100%) 10/10 (100%) |
|POLY-3 RATE (b) | 0/0.10 1/1.09 8/8.02 9/9.01 10/10.00 10/10.00 |
|POLY-3 PERCENT (g) | 0.0% 92.0% 99.8% 99.9% 100.0% 100.0% |
|INT SACRIFICE 1 (c)| 0/10 (0%) 1/10 (10%) 8/10 (80%) 9/10 (90%) 10/10 (100%) 10/10 (100%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 213 (I) 213 (I) 213 (I) 213 (I) 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.500 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.161 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001N** |
|POLY 1.5 | P<0.001 ** P=0.189 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001N** |
|POLY 6 | P<0.001 ** P=0.159 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001N** |
|LOGISTIC REGRESSION| (e) (e) (e) (e) P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.500 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Toxic Hepatopathy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 10/10 (100%) |
|POLY-3 RATE (b) | 0/0.10 0/0.10 0/0.10 0/0.10 0/0.10 10/10.00 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 100.0% |
|INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 10/10 (100%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- --- --- --- --- 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P<0.001 ** |
|POLY 3 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** |
|POLY 1.5 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** |
|POLY 6 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 4
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Hepatocyte |
| Hypertrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/10 (0%) 2/10 (20%) 3/10 (30%) 6/10 (60%) 9/10 (90%) 10/10 (100%) |
|POLY-3 RATE (b) | 0/0.10 2/2.08 3/3.07 6/6.04 9/9.01 10/10.00 |
|POLY-3 PERCENT (g) | 0.0% 96.3% 97.8% 99.4% 99.9% 100.0% |
|INT SACRIFICE 1 (c)| 0/10 (0%) 2/10 (20%) 3/10 (30%) 6/10 (60%) 9/10 (90%) 10/10 (100%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 213 (I) 213 (I) 213 (I) 213 (I) 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.234 P=0.111 P=0.009 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.068 P=0.025 * P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.079 P=0.030 * P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.067 P=0.025 * P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.237 P=0.105 P=0.005 ** P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver: Hepatocyte |
| Multinucleated |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 5/10 (50%) 9/10 (90%) |
|POLY-3 RATE (b) | 0/0.10 0/0.10 0/0.10 0/0.10 5/5.05 9/9.01 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 99.0% 99.9% |
|INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 5/10 (50%) 9/10 (90%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- --- --- --- 213 (I) 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** (e) (e) (e) P=0.022 * P<0.001 ** |
|POLY 3 | P<0.001 ** (e) (e) (e) P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** (e) (e) (e) P=0.002 ** P<0.001 ** |
|POLY 6 | P<0.001 ** (e) (e) (e) P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P=0.016 * P<0.001 ** |
|ORDER RESTRICTED | P=0.002 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 5
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung |
| Infiltration Cellular Histiocyte |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/10 (20%) 3/10 (30%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 1/10 (10%) |
|POLY-3 RATE (b) | 2/2.08 3/3.07 1/1.09 1/1.09 0/0.10 1/1.09 |
|POLY-3 PERCENT (g) | 96.3% 97.8% 92.0% 92.0% 0.0% 92.0% |
|INT SACRIFICE 1 (c)| 2/10 (20%) 3/10 (30%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 1/10 (10%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | 213 (I) 213 (I) 213 (I) 213 (I) --- 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.213N P=0.500 P=0.500N P=0.500N P=0.234N P=0.500N |
|POLY 3 | P=0.151N P=0.354 P=0.301N P=0.301N P=0.068N P=0.301N |
|POLY 1.5 | P=0.155N P=0.368 P=0.320N P=0.320N P=0.079N P=0.320N |
|POLY 6 | P=0.150N P=0.353 P=0.299N P=0.299N P=0.067N P=0.299N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.211N P=0.500 P=0.500N P=0.500N P=0.237N P=0.500N |
|ORDER RESTRICTED | P=0.078N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Ovary |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 9/10 (90%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 7/10 (70%) |
|POLY-3 RATE (b) | 9/9.01 0/0.00 0/0.00 0/0.00 0/0.00 7/7.03 |
|POLY-3 PERCENT (g) | 99.9% 0.0% 0.0% 0.0% 0.0% 99.6% |
|INT SACRIFICE 1 (c)| 9/10 (90%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 7/10 (70%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | 213 (I) --- --- --- --- 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.213N P=1.000 P=1.000 P=1.000 P=1.000 P=0.293N |
|POLY 3 | (e) (e) (e) (e) (e) P=0.254N |
|POLY 1.5 | (e) (e) (e) (e) (e) P=0.257N |
|POLY 6 | (e) (e) (e) (e) (e) P=0.255N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.207N P=1.000 P=1.000 P=1.000 P=1.000 P=0.291N |
|ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 6
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas: Acinus |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/10 (20%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/10 (0%) |
|POLY-3 RATE (b) | 2/2.08 0/0.10 1/1.09 0/0.10 1/1.09 0/0.10 |
|POLY-3 PERCENT (g) | 96.3% 0.0% 92.0% 0.0% 92.0% 0.0% |
|INT SACRIFICE 1 (c)| 2/10 (20%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/10 (0%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | 213 (I) --- 213 (I) --- 213 (I) --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.289N P=0.234N P=0.500N P=0.234N P=0.500N P=0.234N |
|POLY 3 | P=0.176N P=0.068N P=0.301N P=0.068N P=0.301N P=0.068N |
|POLY 1.5 | P=0.178N P=0.079N P=0.320N P=0.079N P=0.320N P=0.079N |
|POLY 6 | P=0.176N P=0.067N P=0.299N P=0.067N P=0.299N P=0.067N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.287N P=0.237N P=0.500N P=0.237N P=0.500N P=0.237N |
|ORDER RESTRICTED | P=0.322N (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas: Acinus |
| Vacuolization Cytoplasmic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 5/10 (50%) |
|POLY-3 RATE (b) | 0/0.10 0/0.10 0/0.10 0/0.10 0/0.10 5/5.05 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 99.0% |
|INT SACRIFICE 1 (c)| 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 5/10 (50%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- --- --- --- --- 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P=0.022 * |
|POLY 3 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** |
|POLY 1.5 | P<0.001 ** (e) (e) (e) (e) P=0.002 ** |
|POLY 6 | P<0.001 ** (e) (e) (e) (e) P<0.001 ** |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P=0.016 * |
|ORDER RESTRICTED | P=0.151 (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 7
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Spleen |
| Pigmentation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 10/10 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 10/10 (100%) |
|POLY-3 RATE (b) | 10/10.00 0/0.00 0/0.00 0/0.00 0/0.00 10/10.00 |
|POLY-3 PERCENT (g) | 100.0% 0.0% 0.0% 0.0% 0.0% 100.0% |
|INT SACRIFICE 1 (c)| 10/10 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 10/10 (100%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | 213 (I) --- --- --- --- 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | (e) (e) (e) (e) (e) (e) |
|POLY 3 | (e) (e) (e) (e) (e) (e) |
|POLY 1.5 | (e) (e) (e) (e) (e) (e) |
|POLY 6 | (e) (e) (e) (e) (e) (e) |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) |
|ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Thymus |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 2/10 (20%) 1/10 (10%) 5/10 (50%) 6/10 (60%) 7/10 (70%) 10/10 (100%) |
|POLY-3 RATE (b) | 2/2.08 1/1.09 5/5.05 6/6.04 7/7.03 10/10.00 |
|POLY-3 PERCENT (g) | 96.3% 92.0% 99.0% 99.4% 99.6% 100.0% |
|INT SACRIFICE 1 (c)| 2/10 (20%) 1/10 (10%) 5/10 (50%) 6/10 (60%) 7/10 (70%) 10/10 (100%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | 213 (I) 213 (I) 213 (I) 213 (I) 213 (I) 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P=0.500N P=0.180 P=0.091 P=0.040 * P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.301N P=0.099 P=0.038 * P=0.010 * P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.320N P=0.106 P=0.041 * P=0.011 * P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.299N P=0.099 P=0.038 * P=0.010 * P<0.001 ** |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P<0.001 ** P=0.500N P=0.175 P=0.085 P=0.035 * P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 8
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: Follicular Cell |
| Hypertrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 0/10 (0%) 3/10 (30%) 3/10 (30%) 3/10 (30%) 4/10 (40%) 6/10 (60%) |
|POLY-3 RATE (b) | 0/0.10 3/3.07 3/3.07 3/3.07 4/4.06 6/6.04 |
|POLY-3 PERCENT (g) | 0.0% 97.8% 97.8% 97.8% 98.6% 99.4% |
|INT SACRIFICE 1 (c)| 0/10 (0%) 3/10 (30%) 3/10 (30%) 3/10 (30%) 4/10 (40%) 6/10 (60%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | --- 213 (I) 213 (I) 213 (I) 213 (I) 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.011 * P=0.111 P=0.111 P=0.111 P=0.051 P=0.009 ** |
|POLY 3 | P=0.007 ** P=0.025 * P=0.025 * P=0.025 * P=0.007 ** P<0.001 ** |
|POLY 1.5 | P=0.007 ** P=0.030 * P=0.030 * P=0.030 * P=0.009 ** P<0.001 ** |
|POLY 6 | P=0.007 ** P=0.025 * P=0.025 * P=0.025 * P=0.007 ** P<0.001 ** |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.011 * P=0.105 P=0.105 P=0.105 P=0.043 * P=0.005 ** |
|ORDER RESTRICTED | P=0.016 * (e) (e) (e) (e) (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus |
| Metaplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 8/10 (80%) 0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 4/10 (40%) |
|POLY-3 RATE (b) | 8/8.02 0/0.01 0/0.00 0/0.00 0/0.00 4/4.06 |
|POLY-3 PERCENT (g) | 99.8% 0.0% 0.0% 0.0% 0.0% 98.6% |
|INT SACRIFICE 1 (c)| 8/10 (80%) 0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 4/10 (40%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | 213 (I) --- --- --- --- 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.103N P=0.305N P=1.000N P=1.000N P=1.000N P=0.091N |
|POLY 3 | (e) P=0.036N* (e) (e) (e) P=0.048N* |
|POLY 1.5 | (e) P=0.046N* (e) (e) (e) P=0.051N |
|POLY 6 | (e) P=0.035N* (e) (e) (e) P=0.048N* |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.098N P=0.273N P=1.000 P=1.000 P=1.000 P=0.085N |
|ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) |
|=================================================================================================================================|
Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 9
Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 143 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus: Endometrium |
| Hyperplasia Cystic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | |
|----------- | |
|OVERALL (a) | 1/10 (10%) 1/1 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/10 (20%) |
|POLY-3 RATE (b) | 1/1.09 1/1.00 0/0.00 0/0.00 0/0.00 2/2.08 |
|POLY-3 PERCENT (g) | 92.0% 100.0% 0.0% 0.0% 0.0% 96.3% |
|INT SACRIFICE 1 (c)| 1/10 (10%) 1/1 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/10 (20%) |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |
|FIRST INCIDENCE | 213 (I) 213 (I) --- --- --- 213 (I) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.565 P=0.205 P=1.000N P=1.000N P=1.000N P=0.500 |
|POLY 3 | (e) P=0.009 ** (e) (e) (e) P=0.301 |
|POLY 1.5 | (e) P=0.020 * (e) (e) (e) P=0.320 |
|POLY 6 | (e) P=0.008 ** (e) (e) (e) P=0.299 |
|LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.567 P=0.182 P=1.000 P=1.000 P=1.000 P=0.500 |
|ORDER RESTRICTED | (e) (e) (e) (e) (e) (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).