TDMS Study 96007-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 11/25/02
EXPERIMENT: 96007 TEST: 03 TIME: 12:47:11
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
------------------------------------------------------------------------------------------------------------------------------------
CONTROL VS HIGH DOSE AND STOP GRP.
REASONS FOR REMOVAL: 25018 Dosing Accident
25019 Moribund Sacrifice
25020 Natural Death
25021 Terminal Sacrifice
REMOVAL DATE RANGE: ALL
TREATMENT GROUPS: INCLUDE 001 0 NG/KG
INCLUDE 006 100 NG/KG
INCLUDE 007 100 NG/ KG/STOP
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 11/25/02
EXPERIMENT: 96007 TEST: 03 TIME: 12:47:11
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
Heart
Islets, Pancreatic
Liver
Lung
Pancreas
Pituitary Gland
Spleen
Thymus
Thyroid Gland
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08
LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 11/25/02
EXPERIMENT: 96007 TEST: 03 TIME: 12:47:11
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
Islets, Pancreatic Carcinoma or Adenoma
Liver Cholangiocarcinoma
Hepatocellular Adenoma
Lung Cystic Keratinizing Epithelioma
Mammary Gland Adenoma
Carcinoma
Carcinoma or Adenoma
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
Pituitary Gland: Pars Intermedia 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: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Pheochromocytoma Benign |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 3/53 (6%) 4/103 (4%) |
|POLY-3 RATE (b) | 3/39.55 4/81.45 |
|POLY-3 PERCENT (g) | 7.6% 4.9% |
|TERMINAL (d) | 3/25 (12%) 0/42 (0%) |
|FIRST INCIDENCE | 731 (T) 642 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.499N P=0.499N |
|POLY 3 | P=0.414N P=0.378N |
|POLY 1.5 | P=0.418N P=0.383N |
|POLY 6 | P=0.417N P=0.382N |
|LOGISTIC REGRESSION| P=0.443N P=0.443N |
|COCH-ARM / FISHERS | P=0.460N P=0.444N |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Pheochromocytoma: Benign, Complex, Malignant, NOS |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 3/53 (6%) 5/103 (5%) |
|POLY-3 RATE (b) | 3/39.55 5/81.45 |
|POLY-3 PERCENT (g) | 7.6% 6.1% |
|TERMINAL (d) | 3/25 (12%) 1/42 (2%) |
|FIRST INCIDENCE | 731 (T) 642 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.609N P=0.609N |
|POLY 3 | P=0.508N P=0.484N |
|POLY 1.5 | P=0.513N P=0.489N |
|POLY 6 | P=0.513N P=0.489N |
|LOGISTIC REGRESSION| P=0.553N P=0.553N |
|COCH-ARM / FISHERS | P=0.566N P=0.550N |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Heart |
| Schwannoma Malignant |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 3/102 (3%) |
|POLY-3 RATE (b) | 0/39.55 3/80.62 |
|POLY-3 PERCENT (g) | 0.0% 3.7% |
|TERMINAL (d) | 0/25 (0%) 1/42 (2%) |
|FIRST INCIDENCE | --- 484 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.259 P=0.259 |
|POLY 3 | P=0.264 P=0.211 |
|POLY 1.5 | P=0.262 P=0.210 |
|POLY 6 | P=0.260 P=0.208 |
|LOGISTIC REGRESSION| P=0.251 P=0.251 |
|COCH-ARM / FISHERS | P=0.259 P=0.282 |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Islets, Pancreatic |
| Carcinoma or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 2/51 (4%) 0/101 (0%) |
|POLY-3 RATE (b) | 2/39.17 0/79.40 |
|POLY-3 PERCENT (g) | 5.1% 0.0% |
|TERMINAL (d) | 1/25 (4%) 0/42 (0%) |
|FIRST INCIDENCE | 645 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.128N P=0.128N |
|POLY 3 | P=0.104N P=0.063N |
|POLY 1.5 | P=0.104N P=0.062N |
|POLY 6 | P=0.107N P=0.066N |
|LOGISTIC REGRESSION| P=0.101N P=0.101N |
|COCH-ARM / FISHERS | P=0.106N P=0.111N |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Cholangiocarcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 27/103 (26%) |
|POLY-3 RATE (b) | 0/39.55 27/83.74 |
|POLY-3 PERCENT (g) | 0.0% 32.2% |
|TERMINAL (d) | 0/25 (0%) 14/42 (33%) |
|FIRST INCIDENCE | --- 610 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hepatocellular Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 13/103 (13%) |
|POLY-3 RATE (b) | 0/39.55 13/82.00 |
|POLY-3 PERCENT (g) | 0.0% 15.9% |
|TERMINAL (d) | 0/25 (0%) 6/42 (14%) |
|FIRST INCIDENCE | --- 561 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.008 ** P=0.008 ** |
|POLY 3 | P=0.015 * P=0.007 ** |
|POLY 1.5 | P=0.015 * P=0.007 ** |
|POLY 6 | P=0.014 * P=0.006 ** |
|LOGISTIC REGRESSION| P=0.009 ** P=0.009 ** |
|COCH-ARM / FISHERS | P=0.008 ** P=0.003 ** |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Lung |
| Cystic Keratinizing Epithelioma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 0/53 (0%) 9/102 (9%) |
|POLY-3 RATE (b) | 0/39.55 9/80.88 |
|POLY-3 PERCENT (g) | 0.0% 11.1% |
|TERMINAL (d) | 0/25 (0%) 4/42 (10%) |
|FIRST INCIDENCE | --- 610 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.029 * P=0.029 * |
|POLY 3 | P=0.045 * P=0.026 * |
|POLY 1.5 | P=0.045 * P=0.026 * |
|POLY 6 | P=0.044 * P=0.025 * |
|LOGISTIC REGRESSION| P=0.033 * P=0.033 * |
|COCH-ARM / FISHERS | P=0.031 * P=0.020 * |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 2/53 (4%) 1/103 (1%) |
|POLY-3 RATE (b) | 2/39.90 1/80.75 |
|POLY-3 PERCENT (g) | 5.0% 1.2% |
|TERMINAL (d) | 1/25 (4%) 1/42 (2%) |
|FIRST INCIDENCE | 631 731 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.308N P=0.308N |
|POLY 3 | P=0.256N P=0.203N |
|POLY 1.5 | P=0.257N P=0.204N |
|POLY 6 | P=0.262N P=0.210N |
|LOGISTIC REGRESSION| P=0.265N P=0.265N |
|COCH-ARM / FISHERS | P=0.277N P=0.266N |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 4/53 (8%) 1/103 (1%) |
|POLY-3 RATE (b) | 4/40.42 1/81.36 |
|POLY-3 PERCENT (g) | 9.9% 1.2% |
|TERMINAL (d) | 2/25 (8%) 0/42 (0%) |
|FIRST INCIDENCE | 469 537 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.047N* P=0.047N* |
|POLY 3 | P=0.045N* P=0.025N* |
|POLY 1.5 | P=0.046N* P=0.025N* |
|POLY 6 | P=0.047N* P=0.026N* |
|LOGISTIC REGRESSION| P=0.045N* P=0.045N* |
|COCH-ARM / FISHERS | P=0.042N* P=0.046N* |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Carcinoma or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 6/53 (11%) 2/103 (2%) |
|POLY-3 RATE (b) | 6/40.77 2/81.36 |
|POLY-3 PERCENT (g) | 14.7% 2.5% |
|TERMINAL (d) | 3/25 (12%) 1/42 (2%) |
|FIRST INCIDENCE | 469 537 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.022N* P=0.022N* |
|POLY 3 | P=0.019N* P=0.009N** |
|POLY 1.5 | P=0.019N* P=0.009N** |
|POLY 6 | P=0.020N* P=0.010N* |
|LOGISTIC REGRESSION| P=0.016N* P=0.016N* |
|COCH-ARM / FISHERS | P=0.016N* P=0.019N* |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Fibroadenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 33/53 (62%) 56/103 (54%) |
|POLY-3 RATE (b) | 33/46.50 56/91.62 |
|POLY-3 PERCENT (g) | 71.0% 61.1% |
|TERMINAL (d) | 16/25 (64%) 25/42 (60%) |
|FIRST INCIDENCE | 185 345 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.397N P=0.397N |
|POLY 3 | P=0.177N P=0.144N |
|POLY 1.5 | P=0.183N P=0.150N |
|POLY 6 | P=0.198N P=0.165N |
|LOGISTIC REGRESSION| P=0.178N P=0.178N |
|COCH-ARM / FISHERS | P=0.220N P=0.220N |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Fibroma, Fibroadenoma or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 35/53 (66%) 56/103 (54%) |
|POLY-3 RATE (b) | 35/46.86 56/91.62 |
|POLY-3 PERCENT (g) | 74.7% 61.1% |
|TERMINAL (d) | 17/25 (68%) 25/42 (60%) |
|FIRST INCIDENCE | 185 345 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.275N P=0.275N |
|POLY 3 | P=0.086N P=0.061N |
|POLY 1.5 | P=0.090N P=0.064N |
|POLY 6 | P=0.103N P=0.076N |
|LOGISTIC REGRESSION| P=0.082N P=0.082N |
|COCH-ARM / FISHERS | P=0.110N P=0.109N |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Fibroma, Fibroadenoma, Carcinoma, or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 35/53 (66%) 57/103 (55%) |
|POLY-3 RATE (b) | 35/46.86 57/92.22 |
|POLY-3 PERCENT (g) | 74.7% 61.8% |
|TERMINAL (d) | 17/25 (68%) 25/42 (60%) |
|FIRST INCIDENCE | 185 345 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.303N P=0.303N |
|POLY 3 | P=0.099N P=0.072N |
|POLY 1.5 | P=0.105N P=0.077N |
|POLY 6 | P=0.114N P=0.085N |
|LOGISTIC REGRESSION| P=0.104N P=0.104N |
|COCH-ARM / FISHERS | P=0.132N P=0.132N |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) |
| Squamous Cell Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 1/53 (2%) 15/103 (15%) |
|POLY-3 RATE (b) | 1/40.42 15/85.73 |
|POLY-3 PERCENT (g) | 2.5% 17.5% |
|TERMINAL (d) | 0/25 (0%) 2/42 (5%) |
|FIRST INCIDENCE | 366 520 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.021 * P=0.021 * |
|POLY 3 | P=0.028 * P=0.015 * |
|POLY 1.5 | P=0.026 * P=0.013 * |
|POLY 6 | P=0.030 * P=0.015 * |
|LOGISTIC REGRESSION| P=0.009 ** P=0.009 ** |
|COCH-ARM / FISHERS | P=0.014 * P=0.009 ** |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) |
| Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 1/53 (2%) 15/103 (15%) |
|POLY-3 RATE (b) | 1/40.42 15/85.73 |
|POLY-3 PERCENT (g) | 2.5% 17.5% |
|TERMINAL (d) | 0/25 (0%) 2/42 (5%) |
|FIRST INCIDENCE | 366 520 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.021 * P=0.021 * |
|POLY 3 | P=0.028 * P=0.015 * |
|POLY 1.5 | P=0.026 * P=0.013 * |
|POLY 6 | P=0.030 * P=0.015 * |
|LOGISTIC REGRESSION| P=0.009 ** P=0.009 ** |
|COCH-ARM / FISHERS | P=0.014 * P=0.009 ** |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Oral Mucosa |
| Squamous Cell Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 1/53 (2%) 15/103 (15%) |
|POLY-3 RATE (b) | 1/40.42 15/85.73 |
|POLY-3 PERCENT (g) | 2.5% 17.5% |
|TERMINAL (d) | 0/25 (0%) 2/42 (5%) |
|FIRST INCIDENCE | 366 520 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.021 * P=0.021 * |
|POLY 3 | P=0.028 * P=0.015 * |
|POLY 1.5 | P=0.026 * P=0.013 * |
|POLY 6 | P=0.030 * P=0.015 * |
|LOGISTIC REGRESSION| P=0.009 ** P=0.009 ** |
|COCH-ARM / FISHERS | P=0.014 * P=0.009 ** |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas |
| Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 0/51 (0%) 3/100 (3%) |
|POLY-3 RATE (b) | 0/38.86 3/78.94 |
|POLY-3 PERCENT (g) | 0.0% 3.8% |
|TERMINAL (d) | 0/25 (0%) 2/42 (5%) |
|FIRST INCIDENCE | --- 641 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.240 P=0.240 |
|POLY 3 | P=0.263 P=0.209 |
|POLY 1.5 | P=0.263 P=0.209 |
|POLY 6 | P=0.258 P=0.205 |
|LOGISTIC REGRESSION| P=0.267 P=0.267 |
|COCH-ARM / FISHERS | P=0.263 P=0.287 |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pancreas |
| Carcinoma or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 0/51 (0%) 4/100 (4%) |
|POLY-3 RATE (b) | 0/38.86 4/78.94 |
|POLY-3 PERCENT (g) | 0.0% 5.1% |
|TERMINAL (d) | 0/25 (0%) 3/42 (7%) |
|FIRST INCIDENCE | --- 641 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.157 P=0.157 |
|POLY 3 | P=0.192 P=0.144 |
|POLY 1.5 | P=0.192 P=0.145 |
|POLY 6 | P=0.186 P=0.140 |
|LOGISTIC REGRESSION| P=0.180 P=0.180 |
|COCH-ARM / FISHERS | P=0.181 P=0.188 |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland: Pars Distalis or Unspecified Site |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 25/53 (47%) 30/102 (29%) |
|POLY-3 RATE (b) | 25/42.82 30/84.00 |
|POLY-3 PERCENT (g) | 58.4% 35.7% |
|TERMINAL (d) | 15/25 (60%) 13/42 (31%) |
|FIRST INCIDENCE | 474 584 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.062N P=0.062N |
|POLY 3 | P=0.015N* P=0.008N** |
|POLY 1.5 | P=0.017N* P=0.009N** |
|POLY 6 | P=0.018N* P=0.010N* |
|LOGISTIC REGRESSION| P=0.009N** P=0.009N** |
|COCH-ARM / FISHERS | P=0.022N* P=0.023N* |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland: Pars Intermedia |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 2/53 (4%) 0/102 (0%) |
|POLY-3 RATE (b) | 2/39.60 0/80.59 |
|POLY-3 PERCENT (g) | 5.1% 0.0% |
|TERMINAL (d) | 1/25 (4%) 0/42 (0%) |
|FIRST INCIDENCE | 717 --- |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.125N P=0.125N |
|POLY 3 | P=0.104N P=0.064N |
|POLY 1.5 | P=0.105N P=0.065N |
|POLY 6 | P=0.105N P=0.065N |
|LOGISTIC REGRESSION| P=0.111N P=0.111N |
|COCH-ARM / FISHERS | P=0.110N P=0.115N |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Skin |
| Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, |
| or Fibrous Histiocytoma |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 1/53 (2%) 3/103 (3%) |
|POLY-3 RATE (b) | 1/40.13 3/81.65 |
|POLY-3 PERCENT (g) | 2.5% 3.7% |
|TERMINAL (d) | 0/25 (0%) 1/42 (2%) |
|FIRST INCIDENCE | 548 394 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.563 P=0.563 |
|POLY 3 | P=0.537 P=0.507 |
|POLY 1.5 | P=0.537 P=0.507 |
|POLY 6 | P=0.530 P=0.500 |
|LOGISTIC REGRESSION| P=0.509 P=0.509 |
|COCH-ARM / FISHERS | P=0.560 P=0.581 |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: C-Cell |
| Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 20/52 (38%) 24/101 (24%) |
|POLY-3 RATE (b) | 20/42.85 24/81.60 |
|POLY-3 PERCENT (g) | 46.7% 29.4% |
|TERMINAL (d) | 10/25 (40%) 13/42 (31%) |
|FIRST INCIDENCE | 474 584 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.094N P=0.094N |
|POLY 3 | P=0.051N P=0.033N* |
|POLY 1.5 | P=0.046N* P=0.029N* |
|POLY 6 | P=0.067N P=0.047N* |
|LOGISTIC REGRESSION| P=0.027N* P=0.027N* |
|COCH-ARM / FISHERS | P=0.043N* P=0.044N* |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: C-Cell |
| Carcinoma or Adenoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | |
|----------- | |
|OVERALL (a) | 21/52 (40%) 25/101 (25%) |
|POLY-3 RATE (b) | 21/42.85 25/81.60 |
|POLY-3 PERCENT (g) | 49.0% 30.6% |
|TERMINAL (d) | 11/25 (44%) 14/42 (33%) |
|FIRST INCIDENCE | 474 584 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.082N P=0.082N |
|POLY 3 | P=0.041N* P=0.025N* |
|POLY 1.5 | P=0.037N* P=0.022N* |
|POLY 6 | P=0.055N P=0.037N* |
|LOGISTIC REGRESSION| P=0.020N* P=0.020N* |
|COCH-ARM / FISHERS | P=0.035N* P=0.036N* |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus |
| Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 0/53 (0%) 3/103 (3%) |
|POLY-3 RATE (b) | 0/39.55 3/80.81 |
|POLY-3 PERCENT (g) | 0.0% 3.7% |
|TERMINAL (d) | 0/25 (0%) 2/42 (5%) |
|FIRST INCIDENCE | --- 716 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.239 P=0.239 |
|POLY 3 | P=0.265 P=0.211 |
|POLY 1.5 | P=0.264 P=0.210 |
|POLY 6 | P=0.260 P=0.207 |
|LOGISTIC REGRESSION| P=0.252 P=0.252 |
|COCH-ARM / FISHERS | P=0.261 P=0.285 |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus |
| Polyp Stromal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 11/53 (21%) 12/103 (12%) |
|POLY-3 RATE (b) | 11/40.11 12/82.21 |
|POLY-3 PERCENT (g) | 27.4% 14.6% |
|TERMINAL (d) | 8/25 (32%) 6/42 (14%) |
|FIRST INCIDENCE | 645 598 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.157N P=0.157N |
|POLY 3 | P=0.088N P=0.060N |
|POLY 1.5 | P=0.093N P=0.065N |
|POLY 6 | P=0.089N P=0.062N |
|LOGISTIC REGRESSION| P=0.081N P=0.081N |
|COCH-ARM / FISHERS | P=0.100N P=0.102N |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|Uterus |
| Squamous Cell Carcinoma |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 0/53 (0%) 2/103 (2%) |
|POLY-3 RATE (b) | 0/39.55 2/80.75 |
|POLY-3 PERCENT (g) | 0.0% 2.5% |
|TERMINAL (d) | 0/25 (0%) 2/42 (5%) |
|FIRST INCIDENCE | --- 731 (T) |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.358 P=0.358 |
|POLY 3 | P=0.373 P=0.314 |
|POLY 1.5 | P=0.372 P=0.313 |
|POLY 6 | P=0.369 P=0.310 |
|LOGISTIC REGRESSION| (e) P=0.358 |
|COCH-ARM / FISHERS | P=0.394 P=0.434 |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 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 | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|All Organs |
| Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, |
| NOS, or Undifferentiated Cell Type |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 0/53 (0%) 3/103 (3%) |
|POLY-3 RATE (b) | 0/39.55 3/81.65 |
|POLY-3 PERCENT (g) | 0.0% 3.7% |
|TERMINAL (d) | 0/25 (0%) 2/42 (5%) |
|FIRST INCIDENCE | --- 345 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.242 P=0.242 |
|POLY 3 | P=0.267 P=0.213 |
|POLY 1.5 | P=0.266 P=0.212 |
|POLY 6 | P=0.263 P=0.209 |
|LOGISTIC REGRESSION| P=0.229 P=0.229 |
|COCH-ARM / FISHERS | P=0.261 P=0.285 |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|All Organs |
| Benign Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 45/53 (85%) 82/103 (80%) |
|POLY-3 RATE (b) | 45/48.82 82/95.84 |
|POLY-3 PERCENT (g) | 92.2% 85.6% |
|TERMINAL (d) | 23/25 (92%) 35/42 (83%) |
|FIRST INCIDENCE | 185 345 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.537N P=0.537N |
|POLY 3 | P=0.182N P=0.145N |
|POLY 1.5 | P=0.193N P=0.157N |
|POLY 6 | P=0.197N P=0.160N |
|LOGISTIC REGRESSION| P=0.140N P=0.140N |
|COCH-ARM / FISHERS | P=0.278N P=0.282N |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 15
Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION
Terminal Sacrifice at 105 weeks
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|All Organs |
| Malignant Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 13/53 (25%) 53/103 (51%) |
|POLY-3 RATE (b) | 13/43.94 53/91.48 |
|POLY-3 PERCENT (g) | 29.6% 57.9% |
|TERMINAL (d) | 4/25 (16%) 23/42 (55%) |
|FIRST INCIDENCE | 169 345 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.003 ** P=0.003 ** |
|POLY 3 | P=0.003 ** P<0.001 ** |
|POLY 1.5 | P=0.003 ** P<0.001 ** |
|POLY 6 | P=0.003 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** |
|ORDER RESTRICTED | P<0.001 ** (e) |
|=================================================================================================================================|
| | |
| | Females |
|Dose | 0 NG/KG 100 |
| | NG/KG |
|=================================================================================================================================|
| |
|All Organs |
| Malignant and Benign Tumors |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES | # # |
|----------- | |
|OVERALL (a) | 47/53 (89%) 96/103 (93%) |
|POLY-3 RATE (b) | 47/50.68 96/100.4 |
|POLY-3 PERCENT (g) | 92.7% 95.6% |
|TERMINAL (d) | 23/25 (92%) 39/42 (93%) |
|FIRST INCIDENCE | 169 345 |
|-------------------| |
|STATISTICAL TESTS | |
|-------------------| |
|LIFE TABLE | P=0.261 P=0.261 |
|POLY 3 | P=0.342 P=0.302 |
|POLY 1.5 | P=0.293 P=0.253 |
|POLY 6 | P=0.408 P=0.370 |
|LOGISTIC REGRESSION| P=0.346 P=0.346 |
|COCH-ARM / FISHERS | P=0.254 P=0.249 |
|ORDER RESTRICTED | P<0.001 ** (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).