TDMS Study 96007-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 09/30/03 EXPERIMENT: 96007 TEST: 03 TIME: 08:52:44 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 ------------------------------------------------------------------------------------------------------------------------------------ FINAL # 3 RATS CONTROL VS TREATED 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 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 PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 09/30/03 EXPERIMENT: 96007 TEST: 03 TIME: 08:52:44 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 Thyroid Gland Urinary Bladder NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 09/30/03 EXPERIMENT: 96007 TEST: 03 TIME: 08:52:44 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 ----- ---------- Liver Cholangiocarcinoma Hepatocellular Adenoma Hepatocholangioma Lung Cystic Keratinizing Epithelioma Mammary Gland 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 Thyroid Gland: C-Cell Adenoma Carcinoma or Adenoma Uterus Polyp Stromal Squamous Cell Carcinoma All Organs Benign Tumors Malignant Tumors Malignant and Benign Tumors =============================================================== Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 0/54 (0%) 2/53 (4%) 2/53 (4%) 1/53 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 1/39.55 0/34.61 2/38.75 2/34.53 1/39.00 1/42.90 | |POLY-3 PERCENT (g) | 2.5% 0.0% 5.2% 5.8% 2.6% 2.3% | |TERMINAL (d) | 1/25 (4%) 0/21 (0%) 2/23 (9%) 1/19 (5%) 1/22 (5%) 0/21 (0%) | |FIRST INCIDENCE | 731 (T) --- 731 (T) 626 731 (T) 648 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.609N P=0.535N P=0.471 P=0.403 P=0.734 P=0.744 | |POLY 3 | P=0.549N P=0.527N P=0.493 P=0.453 P=0.758 P=0.743N | |POLY 1.5 | P=0.567N P=0.514N P=0.490 P=0.472 P=0.759 P=0.745N | |POLY 6 | P=0.542N P=0.539N P=0.494 P=0.430 P=0.755 P=0.747N | |LOGISTIC REGRESSION| P=0.560N (e) P=0.471 P=0.433 P=0.734 P=0.749N | |COCH-ARM / FISHERS | P=0.614N P=0.495N P=0.500 P=0.500 P=0.752N P=0.752N | |ORDER RESTRICTED | P=0.450 (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 | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma Benign | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 2/54 (4%) 2/53 (4%) 3/53 (6%) 3/53 (6%) 3/53 (6%) | |POLY-3 RATE (b) | 3/39.55 2/34.61 2/38.75 3/34.16 3/39.09 3/43.18 | |POLY-3 PERCENT (g) | 7.6% 5.8% 5.2% 8.8% 7.7% 7.0% | |TERMINAL (d) | 3/25 (12%) 2/21 (10%) 2/23 (9%) 3/19 (16%) 2/22 (9%) 0/21 (0%) | |FIRST INCIDENCE | 731 (T) 731 (T) 731 (T) 731 (T) 708 642 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.414 P=0.581N P=0.539N P=0.532 P=0.604 P=0.606 | |POLY 3 | P=0.542 P=0.561N P=0.509N P=0.594 P=0.658 P=0.622N | |POLY 1.5 | P=0.516 P=0.533N P=0.512N P=0.623 P=0.660 P=0.629N | |POLY 6 | P=0.550 P=0.590N P=0.508N P=0.557 P=0.653 P=0.628N | |LOGISTIC REGRESSION| P=0.492 P=0.581N P=0.539N P=0.532 P=0.618 P=0.642N | |COCH-ARM / FISHERS | P=0.436 P=0.491N P=0.500N P=0.661N P=0.661N P=0.661N | |ORDER RESTRICTED | P=0.688 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Pheochromocytoma: Benign, Complex, Malignant, NOS | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 2/54 (4%) 2/53 (4%) 3/53 (6%) 3/53 (6%) 3/53 (6%) | |POLY-3 RATE (b) | 3/39.55 2/34.61 2/38.75 3/34.16 3/39.09 3/43.18 | |POLY-3 PERCENT (g) | 7.6% 5.8% 5.2% 8.8% 7.7% 7.0% | |TERMINAL (d) | 3/25 (12%) 2/21 (10%) 2/23 (9%) 3/19 (16%) 2/22 (9%) 0/21 (0%) | |FIRST INCIDENCE | 731 (T) 731 (T) 731 (T) 731 (T) 708 642 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.414 P=0.581N P=0.539N P=0.532 P=0.604 P=0.606 | |POLY 3 | P=0.542 P=0.561N P=0.509N P=0.594 P=0.658 P=0.622N | |POLY 1.5 | P=0.516 P=0.533N P=0.512N P=0.623 P=0.660 P=0.629N | |POLY 6 | P=0.550 P=0.590N P=0.508N P=0.557 P=0.653 P=0.628N | |LOGISTIC REGRESSION| P=0.492 P=0.581N P=0.539N P=0.532 P=0.618 P=0.642N | |COCH-ARM / FISHERS | P=0.436 P=0.491N P=0.500N P=0.661N P=0.661N P=0.661N | |ORDER RESTRICTED | P=0.688 (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 | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/51 (2%) 0/54 (0%) 2/53 (4%) 0/53 (0%) 0/52 (0%) 0/52 (0%) | |POLY-3 RATE (b) | 1/38.86 0/34.61 2/38.75 0/34.16 0/38.45 0/41.64 | |POLY-3 PERCENT (g) | 2.6% 0.0% 5.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/25 (4%) 0/21 (0%) 2/23 (9%) 0/19 (0%) 0/22 (0%) 0/21 (0%) | |FIRST INCIDENCE | 731 (T) --- 731 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.248N P=0.535N P=0.471 P=0.555N P=0.525N P=0.535N | |POLY 3 | P=0.205N P=0.523N P=0.499 P=0.526N P=0.502N P=0.486N | |POLY 1.5 | P=0.218N P=0.509N P=0.499 P=0.512N P=0.500N P=0.486N | |POLY 6 | P=0.196N P=0.537N P=0.497 P=0.542N P=0.506N P=0.493N | |LOGISTIC REGRESSION| P=0.248N (e) P=0.471 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.236N P=0.486N P=0.515 P=0.490N P=0.495N P=0.495N | |ORDER RESTRICTED | P=0.245N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Islets, Pancreatic | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/51 (4%) 0/54 (0%) 2/53 (4%) 0/53 (0%) 0/52 (0%) 0/52 (0%) | |POLY-3 RATE (b) | 2/39.17 0/34.61 2/38.75 0/34.16 0/38.45 0/41.64 | |POLY-3 PERCENT (g) | 5.1% 0.0% 5.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/25 (4%) 0/21 (0%) 2/23 (9%) 0/19 (0%) 0/22 (0%) 0/21 (0%) | |FIRST INCIDENCE | 645 --- 731 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.149N P=0.302N P=0.662 P=0.318N P=0.260N P=0.265N | |POLY 3 | P=0.115N P=0.265N P=0.691 P=0.268N P=0.241N P=0.223N | |POLY 1.5 | P=0.126N P=0.248N P=0.692 P=0.252N P=0.238N P=0.223N | |POLY 6 | P=0.107N P=0.285N P=0.687 P=0.291N P=0.246N P=0.232N | |LOGISTIC REGRESSION| P=0.133N P=0.263N P=0.693 P=0.267N P=0.239N P=0.224N | |COCH-ARM / FISHERS | P=0.144N P=0.234N P=0.676N P=0.238N P=0.243N P=0.243N | |ORDER RESTRICTED | P=0.053N (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 | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Nephroblastoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/54 (4%) 1/53 (2%) 0/53 (0%) 0/53 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 0/39.55 2/36.54 1/39.71 0/34.16 0/39.00 0/42.60 | |POLY-3 PERCENT (g) | 0.0% 5.5% 2.5% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- 200 240 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.212N P=0.248 P=0.492 (e) (e) (e) | |POLY 3 | P=0.218N P=0.219 P=0.501 (e) (e) (e) | |POLY 1.5 | P=0.215N P=0.230 P=0.498 (e) (e) (e) | |POLY 6 | P=0.224N P=0.208 P=0.502 (e) (e) (e) | |LOGISTIC REGRESSION| P=0.374N P=0.189 P=0.663 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.215N P=0.252 P=0.500 (e) (e) (e) | |ORDER RESTRICTED | P=0.243N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Cholangiocarcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 1/53 (2%) 4/53 (8%) 25/53 (47%) | |POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 1/34.63 4/39.00 25/45.58 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.9% 10.3% 54.9% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 4/22 (18%) 13/21 (62%) | |FIRST INCIDENCE | --- --- --- 592 731 (T) 610 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P=0.462 P=0.046 * P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P=0.474 P=0.057 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P=0.484 P=0.059 P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P=0.461 P=0.055 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.508 P=0.046 * P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.500 P=0.059 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 | | Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 1/53 (2%) 13/53 (25%) | |POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 0/34.16 1/39.04 13/43.52 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 2.6% 29.9% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 7/21 (33%) | |FIRST INCIDENCE | --- --- --- --- 720 642 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) P=0.476 P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) (e) P=0.497 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) (e) P=0.499 P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) (e) P=0.494 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) P=0.487 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P=0.500 P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Hepatocholangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 0/34.16 0/39.00 2/42.93 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 4.7% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 1/21 (5%) | |FIRST INCIDENCE | --- --- --- --- --- 638 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.015 * (e) (e) (e) (e) P=0.229 | |POLY 3 | P=0.012 * (e) (e) (e) (e) P=0.256 | |POLY 1.5 | P=0.012 * (e) (e) (e) (e) P=0.253 | |POLY 6 | P=0.012 * (e) (e) (e) (e) P=0.251 | |LOGISTIC REGRESSION| P=0.015 * (e) (e) (e) (e) P=0.251 | |COCH-ARM / FISHERS | P=0.011 * (e) (e) (e) (e) P=0.248 | |ORDER RESTRICTED | P=0.011 * (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 | |=================================================================================================================================| | | |Lung | | Cystic Keratinizing Epithelioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 0/52 (0%) 0/53 (0%) 9/52 (17%) | |POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 0/33.71 0/39.00 9/42.72 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 21.1% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 4/21 (19%) | |FIRST INCIDENCE | --- --- --- --- --- 610 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P=0.002 ** | |POLY 3 | P<0.001 ** (e) (e) (e) (e) P=0.002 ** | |POLY 1.5 | P<0.001 ** (e) (e) (e) (e) P=0.002 ** | |POLY 6 | P<0.001 ** (e) (e) (e) (e) P=0.002 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) (e) P=0.003 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 2/53 (4%) 0/54 (0%) 1/53 (2%) 0/53 (0%) 0/53 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 2/39.90 0/34.61 1/38.75 0/34.16 0/39.00 1/42.60 | |POLY-3 PERCENT (g) | 5.0% 0.0% 2.6% 0.0% 0.0% 2.4% | |TERMINAL (d) | 1/25 (4%) 0/21 (0%) 1/23 (4%) 0/19 (0%) 0/22 (0%) 1/21 (5%) | |FIRST INCIDENCE | 631 --- 731 (T) --- --- 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.591N P=0.305N P=0.532N P=0.317N P=0.260N P=0.535N | |POLY 3 | P=0.555N P=0.270N P=0.510N P=0.273N P=0.242N P=0.477N | |POLY 1.5 | P=0.570N P=0.254N P=0.511N P=0.258N P=0.240N P=0.479N | |POLY 6 | P=0.541N P=0.288N P=0.512N P=0.293N P=0.247N P=0.488N | |LOGISTIC REGRESSION| P=0.555N P=0.263N P=0.507N P=0.267N P=0.240N P=0.479N | |COCH-ARM / FISHERS | P=0.595N P=0.243N P=0.500N P=0.248N P=0.248N P=0.500N | |ORDER RESTRICTED | P=0.110N (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 | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 4/53 (8%) 8/54 (15%) 4/53 (8%) 2/53 (4%) 2/53 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 4/40.42 8/37.03 4/39.08 2/35.28 2/39.22 0/42.60 | |POLY-3 PERCENT (g) | 9.9% 21.6% 10.2% 5.7% 5.1% 0.0% | |TERMINAL (d) | 2/25 (8%) 4/21 (19%) 1/23 (4%) 0/19 (0%) 1/22 (5%) 0/21 (0%) | |FIRST INCIDENCE | 469 241 659 338 673 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.008N** P=0.127 P=0.616 P=0.439N P=0.377N P=0.077N | |POLY 3 | P=0.004N** P=0.132 P=0.626 P=0.401N P=0.350N P=0.053N | |POLY 1.5 | P=0.004N** P=0.155 P=0.624 P=0.374N P=0.345N P=0.054N | |POLY 6 | P=0.004N** P=0.109 P=0.627 P=0.436N P=0.360N P=0.057N | |LOGISTIC REGRESSION| P=0.006N** P=0.184 P=0.633 P=0.327N P=0.340N P=0.060N | |COCH-ARM / FISHERS | P=0.006N** P=0.189 P=0.642N P=0.339N P=0.339N P=0.059N | |ORDER RESTRICTED | P=0.005N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 6/53 (11%) 8/54 (15%) 5/53 (9%) 2/53 (4%) 2/53 (4%) 1/53 (2%) | |POLY-3 RATE (b) | 6/40.77 8/37.03 5/39.08 2/35.28 2/39.22 1/42.60 | |POLY-3 PERCENT (g) | 14.7% 21.6% 12.8% 5.7% 5.1% 2.4% | |TERMINAL (d) | 3/25 (12%) 4/21 (19%) 2/23 (9%) 0/19 (0%) 1/22 (5%) 1/21 (5%) | |FIRST INCIDENCE | 469 241 659 338 673 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.011N* P=0.278 P=0.538N P=0.232N P=0.168N P=0.077N | |POLY 3 | P=0.005N** P=0.310 P=0.530N P=0.182N P=0.143N P=0.048N* | |POLY 1.5 | P=0.006N** P=0.350 P=0.528N P=0.160N P=0.139N P=0.048N* | |POLY 6 | P=0.005N** P=0.266 P=0.536N P=0.214N P=0.151N P=0.053N | |LOGISTIC REGRESSION| P=0.007N** P=0.385 P=0.515N P=0.137N P=0.137N P=0.051N | |COCH-ARM / FISHERS | P=0.009N** P=0.402 P=0.500N P=0.135N P=0.135N P=0.056N | |ORDER RESTRICTED | P=0.009N** (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 | |=================================================================================================================================| | | |Mammary Gland | | Fibroadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 33/53 (62%) 40/54 (74%) 34/53 (64%) 29/53 (55%) 36/53 (68%) 24/53 (45%) | |POLY-3 RATE (b) | 33/46.50 40/48.95 34/45.82 29/41.25 36/48.31 24/47.04 | |POLY-3 PERCENT (g) | 71.0% 81.7% 74.2% 70.3% 74.5% 51.0% | |TERMINAL (d) | 16/25 (64%) 16/21 (76%) 16/23 (70%) 12/19 (63%) 15/22 (68%) 12/21 (57%) | |FIRST INCIDENCE | 185 241 236 453 141 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.021N* P=0.048 * P=0.404 P=0.338 P=0.256 P=0.174N | |POLY 3 | P<0.001N** P=0.147 P=0.452 P=0.570N P=0.435 P=0.031N* | |POLY 1.5 | P<0.001N** P=0.129 P=0.418 P=0.468N P=0.401 P=0.033N* | |POLY 6 | P=0.002N** P=0.183 P=0.498 P=0.559 P=0.453 P=0.041N* | |LOGISTIC REGRESSION| P=0.002N** P=0.104 P=0.445 P=0.424N P=0.337 P=0.043N* | |COCH-ARM / FISHERS | P=0.009N** P=0.135 P=0.500 P=0.277N P=0.342 P=0.059N | |ORDER RESTRICTED | P=0.002N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 35/53 (66%) 40/54 (74%) 35/53 (66%) 29/53 (55%) 36/53 (68%) 24/53 (45%) | |POLY-3 RATE (b) | 35/46.86 40/48.95 35/45.82 29/41.25 36/48.31 24/47.04 | |POLY-3 PERCENT (g) | 74.7% 81.7% 76.4% 70.3% 74.5% 51.0% | |TERMINAL (d) | 17/25 (68%) 16/21 (76%) 17/23 (74%) 12/19 (63%) 15/22 (68%) 12/21 (57%) | |FIRST INCIDENCE | 185 241 236 453 141 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.013N* P=0.079 P=0.454 P=0.435 P=0.352 P=0.109N | |POLY 3 | P<0.001N** P=0.269 P=0.522 P=0.407N P=0.589N P=0.010N* | |POLY 1.5 | P<0.001N** P=0.244 P=0.493 P=0.308N P=0.572 P=0.011N* | |POLY 6 | P<0.001N** P=0.311 P=0.554 P=0.500N P=0.591N P=0.015N* | |LOGISTIC REGRESSION| P<0.001N** P=0.192 P=0.523 P=0.275N P=0.495 P=0.016N* | |COCH-ARM / FISHERS | P=0.004N** P=0.243 P=0.581N P=0.160N P=0.500 P=0.025N* | |ORDER RESTRICTED | P<0.001N** (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 | |=================================================================================================================================| | | |Mammary Gland | | Fibroma, Fibroadenoma, Carcinoma, or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 35/53 (66%) 43/54 (80%) 37/53 (70%) 31/53 (58%) 37/53 (70%) 24/53 (45%) | |POLY-3 RATE (b) | 35/46.86 43/49.90 37/46.14 31/42.36 37/48.53 24/47.04 | |POLY-3 PERCENT (g) | 74.7% 86.2% 80.2% 73.2% 76.2% 51.0% | |TERMINAL (d) | 17/25 (68%) 17/21 (81%) 17/23 (74%) 12/19 (63%) 15/22 (68%) 12/21 (57%) | |FIRST INCIDENCE | 185 241 236 338 141 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.007N** P=0.034 * P=0.344 P=0.318 P=0.303 P=0.109N | |POLY 3 | P<0.001N** P=0.107 P=0.343 P=0.533N P=0.526 P=0.010N* | |POLY 1.5 | P<0.001N** P=0.089 P=0.314 P=0.441N P=0.488 P=0.011N* | |POLY 6 | P<0.001N** P=0.135 P=0.389 P=0.606 P=0.546 P=0.015N* | |LOGISTIC REGRESSION| P<0.001N** P=0.062 P=0.349 P=0.411N P=0.412 P=0.016N* | |COCH-ARM / FISHERS | P<0.001N** P=0.086 P=0.418 P=0.274N P=0.418 P=0.025N* | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) | | Squamous Cell Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 1/53 (2%) 2/54 (4%) 1/53 (2%) 0/53 (0%) 4/53 (8%) 10/53 (19%) | |POLY-3 RATE (b) | 1/40.42 2/34.91 1/39.25 0/34.16 4/39.40 10/45.45 | |POLY-3 PERCENT (g) | 2.5% 5.7% 2.6% 0.0% 10.2% 22.0% | |TERMINAL (d) | 0/25 (0%) 1/21 (5%) 0/23 (0%) 0/19 (0%) 1/22 (5%) 2/21 (10%) | |FIRST INCIDENCE | 366 647 578 --- 659 546 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.444 P=0.757N P=0.496N P=0.166 P=0.009 ** | |POLY 3 | P<0.001 ** P=0.449 P=0.755 P=0.533N P=0.169 P=0.007 ** | |POLY 1.5 | P<0.001 ** P=0.471 P=0.753 P=0.520N P=0.173 P=0.006 ** | |POLY 6 | P<0.001 ** P=0.428 P=0.756 P=0.549N P=0.165 P=0.007 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.527 P=0.725N P=0.436N P=0.180 P=0.002 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.507 P=0.752N P=0.500N P=0.181 P=0.004 ** | |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 | |=================================================================================================================================| | | |Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva) | | Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 1/53 (2%) 2/54 (4%) 1/53 (2%) 0/53 (0%) 4/53 (8%) 10/53 (19%) | |POLY-3 RATE (b) | 1/40.42 2/34.91 1/39.25 0/34.16 4/39.40 10/45.45 | |POLY-3 PERCENT (g) | 2.5% 5.7% 2.6% 0.0% 10.2% 22.0% | |TERMINAL (d) | 0/25 (0%) 1/21 (5%) 0/23 (0%) 0/19 (0%) 1/22 (5%) 2/21 (10%) | |FIRST INCIDENCE | 366 647 578 --- 659 546 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.444 P=0.757N P=0.496N P=0.166 P=0.009 ** | |POLY 3 | P<0.001 ** P=0.449 P=0.755 P=0.533N P=0.169 P=0.007 ** | |POLY 1.5 | P<0.001 ** P=0.471 P=0.753 P=0.520N P=0.173 P=0.006 ** | |POLY 6 | P<0.001 ** P=0.428 P=0.756 P=0.549N P=0.165 P=0.007 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.527 P=0.725N P=0.436N P=0.180 P=0.002 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.507 P=0.752N P=0.500N P=0.181 P=0.004 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Oral Mucosa | | Squamous Cell Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 1/53 (2%) 2/54 (4%) 1/53 (2%) 0/53 (0%) 4/53 (8%) 10/53 (19%) | |POLY-3 RATE (b) | 1/40.42 2/34.91 1/39.25 0/34.16 4/39.40 10/45.45 | |POLY-3 PERCENT (g) | 2.5% 5.7% 2.6% 0.0% 10.2% 22.0% | |TERMINAL (d) | 0/25 (0%) 1/21 (5%) 0/23 (0%) 0/19 (0%) 1/22 (5%) 2/21 (10%) | |FIRST INCIDENCE | 366 647 578 --- 659 546 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.444 P=0.757N P=0.496N P=0.166 P=0.009 ** | |POLY 3 | P<0.001 ** P=0.449 P=0.755 P=0.533N P=0.169 P=0.007 ** | |POLY 1.5 | P<0.001 ** P=0.471 P=0.753 P=0.520N P=0.173 P=0.006 ** | |POLY 6 | P<0.001 ** P=0.428 P=0.756 P=0.549N P=0.165 P=0.007 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.527 P=0.725N P=0.436N P=0.180 P=0.002 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.507 P=0.752N P=0.500N P=0.181 P=0.004 ** | |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 | |=================================================================================================================================| | | |Pancreas | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/54 (0%) 0/52 (0%) 0/53 (0%) 0/52 (0%) 2/51 (4%) | |POLY-3 RATE (b) | 0/38.86 0/34.61 0/38.64 0/34.16 0/38.45 2/41.18 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 4.9% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 1/21 (5%) | |FIRST INCIDENCE | --- --- --- --- --- 641 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.014 * (e) (e) (e) (e) P=0.223 | |POLY 3 | P=0.011 * (e) (e) (e) (e) P=0.250 | |POLY 1.5 | P=0.011 * (e) (e) (e) (e) P=0.249 | |POLY 6 | P=0.011 * (e) (e) (e) (e) P=0.244 | |LOGISTIC REGRESSION| P=0.014 * (e) (e) (e) (e) P=0.247 | |COCH-ARM / FISHERS | P=0.010 * (e) (e) (e) (e) P=0.248 | |ORDER RESTRICTED | P=0.011 * (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pancreas | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/54 (0%) 0/52 (0%) 0/53 (0%) 0/52 (0%) 3/51 (6%) | |POLY-3 RATE (b) | 0/38.86 0/34.61 0/38.64 0/34.16 0/38.45 3/41.18 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 7.3% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 2/21 (10%) | |FIRST INCIDENCE | --- --- --- --- --- 641 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P=0.104 | |POLY 3 | P<0.001 ** (e) (e) (e) (e) P=0.129 | |POLY 1.5 | P<0.001 ** (e) (e) (e) (e) P=0.128 | |POLY 6 | P<0.001 ** (e) (e) (e) (e) P=0.123 | |LOGISTIC REGRESSION| P=0.002 ** (e) (e) (e) (e) P=0.125 | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) (e) P=0.121 | |ORDER RESTRICTED | P=0.002 ** (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 | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 25/53 (47%) 20/54 (37%) 26/52 (50%) 15/53 (28%) 20/53 (38%) 11/52 (21%) | |POLY-3 RATE (b) | 25/42.82 20/36.20 26/40.49 15/36.38 20/42.25 11/44.01 | |POLY-3 PERCENT (g) | 58.4% 55.3% 64.2% 41.2% 47.3% 25.0% | |TERMINAL (d) | 15/25 (60%) 16/21 (76%) 15/23 (65%) 9/19 (47%) 10/22 (46%) 4/21 (19%) | |FIRST INCIDENCE | 474 604 550 545 444 604 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004N** P=0.542N P=0.397 P=0.253N P=0.356N P=0.016N* | |POLY 3 | P<0.001N** P=0.478N P=0.369 P=0.087N P=0.202N P<0.001N** | |POLY 1.5 | P<0.001N** P=0.334N P=0.372 P=0.056N P=0.203N P<0.001N** | |POLY 6 | P<0.001N** P=0.545 P=0.363 P=0.146N P=0.212N P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P=0.503N P=0.420 P=0.102N P=0.216N P<0.001N** | |COCH-ARM / FISHERS | P=0.003N** P=0.193N P=0.462 P=0.035N* P=0.216N P=0.004N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Intermedia | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/54 (0%) 0/52 (0%) 0/53 (0%) 0/53 (0%) 0/52 (0%) | |POLY-3 RATE (b) | 2/39.60 0/34.61 0/38.01 0/34.16 0/39.00 0/42.44 | |POLY-3 PERCENT (g) | 5.1% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/25 (4%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) | |FIRST INCIDENCE | 717 --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.259N P=0.277N P=0.245N P=0.311N P=0.272N P=0.268N | |POLY 3 | P=0.226N P=0.268N P=0.246N P=0.271N P=0.240N P=0.222N | |POLY 1.5 | P=0.235N P=0.253N P=0.248N P=0.257N P=0.239N P=0.225N | |POLY 6 | P=0.216N P=0.284N P=0.244N P=0.290N P=0.244N P=0.226N | |LOGISTIC REGRESSION| P=0.243N P=0.286N P=0.242N P=0.303N P=0.254N P=0.246N | |COCH-ARM / FISHERS | P=0.250N P=0.243N P=0.252N P=0.248N P=0.248N P=0.252N | |ORDER RESTRICTED | P=0.007N** (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 | |=================================================================================================================================| | | |Skin | | Fibroma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 1/53 (2%) 0/54 (0%) 2/53 (4%) 0/53 (0%) 0/53 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 1/40.13 0/34.61 2/39.56 0/34.16 0/39.00 1/42.65 | |POLY-3 PERCENT (g) | 2.5% 0.0% 5.1% 0.0% 0.0% 2.3% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) | |FIRST INCIDENCE | 548 --- 578 --- --- 717 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.605N P=0.505N P=0.509 P=0.515N P=0.490N P=0.747N | |POLY 3 | P=0.612N P=0.529N P=0.495 P=0.532N P=0.506N P=0.747N | |POLY 1.5 | P=0.628N P=0.516N P=0.491 P=0.519N P=0.503N P=0.748N | |POLY 6 | P=0.601N P=0.544N P=0.499 P=0.548N P=0.511N P=0.755N | |LOGISTIC REGRESSION| P=0.653 P=0.475N P=0.511 P=0.479N P=0.497N P=0.753 | |COCH-ARM / FISHERS | P=0.650N P=0.495N P=0.500 P=0.500N P=0.500N P=0.752N | |ORDER RESTRICTED | P=0.480N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, | | or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 1/53 (2%) 0/54 (0%) 3/53 (6%) 1/53 (2%) 0/53 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 1/40.13 0/34.61 3/39.97 1/34.16 0/39.00 1/42.65 | |POLY-3 PERCENT (g) | 2.5% 0.0% 7.5% 2.9% 0.0% 2.3% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 1/19 (5%) 0/22 (0%) 0/21 (0%) | |FIRST INCIDENCE | 548 --- 578 731 (T) --- 717 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.451N P=0.505N P=0.313 P=0.721 P=0.490N P=0.747N | |POLY 3 | P=0.439N P=0.529N P=0.303 P=0.724 P=0.506N P=0.747N | |POLY 1.5 | P=0.458N P=0.516N P=0.298 P=0.740 P=0.503N P=0.748N | |POLY 6 | P=0.430N P=0.544N P=0.309 P=0.704 P=0.511N P=0.755N | |LOGISTIC REGRESSION| P=0.482N P=0.475N P=0.314 P=0.755 P=0.497N P=0.753 | |COCH-ARM / FISHERS | P=0.493N P=0.495N P=0.309 P=0.752N P=0.500N P=0.752N | |ORDER RESTRICTED | P=0.459N (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 | |=================================================================================================================================| | | |Skin | | Schwannoma Malignant | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 1/53 (2%) 0/54 (0%) 0/53 (0%) 2/53 (4%) 0/53 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 1/39.67 0/34.61 0/38.75 2/35.78 0/39.00 1/43.05 | |POLY-3 PERCENT (g) | 2.5% 0.0% 0.0% 5.6% 0.0% 2.3% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) | |FIRST INCIDENCE | 701 --- --- 380 --- 599 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.559 P=0.539N P=0.500N P=0.459 P=0.515N P=0.747N | |POLY 3 | P=0.576 P=0.527N P=0.505N P=0.464 P=0.503N P=0.743N | |POLY 1.5 | P=0.563 P=0.515N P=0.506N P=0.479 P=0.502N P=0.745N | |POLY 6 | P=0.577 P=0.541N P=0.505N P=0.443 P=0.507N P=0.748N | |LOGISTIC REGRESSION| P=0.441 P=0.536N P=0.504N P=0.552 P=0.505N P=0.763 | |COCH-ARM / FISHERS | P=0.519 P=0.495N P=0.500N P=0.500 P=0.500N P=0.752N | |ORDER RESTRICTED | P=0.501 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Carcinoma or Papilloma Squamous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 1/53 (2%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) 1/53 (2%) | |POLY-3 RATE (b) | 1/39.86 0/34.61 0/38.75 0/34.16 2/39.21 1/42.60 | |POLY-3 PERCENT (g) | 2.5% 0.0% 0.0% 0.0% 5.1% 2.4% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 1/21 (5%) | |FIRST INCIDENCE | 646 --- --- --- 701 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.274 P=0.570N P=0.523N P=0.586N P=0.472 P=0.738 | |POLY 3 | P=0.326 P=0.528N P=0.506N P=0.531N P=0.494 P=0.746N | |POLY 1.5 | P=0.310 P=0.515N P=0.506N P=0.518N P=0.497 P=0.747N | |POLY 6 | P=0.328 P=0.542N P=0.506N P=0.547N P=0.488 P=0.754N | |LOGISTIC REGRESSION| P=0.299 P=0.508N P=0.502N P=0.511N P=0.495 P=0.749N | |COCH-ARM / FISHERS | P=0.259 P=0.495N P=0.500N P=0.500N P=0.500 P=0.752N | |ORDER RESTRICTED | P=0.249 (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 | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 20/52 (38%) 15/54 (28%) 17/53 (32%) 16/51 (31%) 13/53 (25%) 11/52 (21%) | |POLY-3 RATE (b) | 20/42.85 15/37.10 17/39.42 16/37.06 13/41.12 11/43.05 | |POLY-3 PERCENT (g) | 46.7% 40.4% 43.1% 43.2% 31.6% 25.6% | |TERMINAL (d) | 10/25 (40%) 10/21 (48%) 13/23 (57%) 8/19 (42%) 8/22 (36%) 6/21 (29%) | |FIRST INCIDENCE | 474 462 626 338 486 638 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.048N* P=0.422N P=0.430N P=0.551 P=0.180N P=0.091N | |POLY 3 | P=0.010N* P=0.366N P=0.459N P=0.464N P=0.111N P=0.030N* | |POLY 1.5 | P=0.015N* P=0.268N P=0.413N P=0.382N P=0.099N P=0.028N* | |POLY 6 | P=0.010N* P=0.499N P=0.533N P=0.579N P=0.139N P=0.043N* | |LOGISTIC REGRESSION| P=0.014N* P=0.286N P=0.338N P=0.385N P=0.093N P=0.028N* | |COCH-ARM / FISHERS | P=0.047N* P=0.168N P=0.316N P=0.292N P=0.092N P=0.043N* | |ORDER RESTRICTED | P=0.021N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 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 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 1/54 (2%) 0/53 (0%) 0/51 (0%) 2/53 (4%) 0/52 (0%) | |POLY-3 RATE (b) | 1/38.90 1/35.04 0/38.75 0/33.58 2/39.00 0/41.66 | |POLY-3 PERCENT (g) | 2.6% 2.9% 0.0% 0.0% 5.1% 0.0% | |TERMINAL (d) | 1/25 (4%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 2/22 (9%) 0/21 (0%) | |FIRST INCIDENCE | 731 (T) 604 --- --- 731 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.506N P=0.712 P=0.517N P=0.555N P=0.455 P=0.535N | |POLY 3 | P=0.468N P=0.738 P=0.501N P=0.529N P=0.501 P=0.486N | |POLY 1.5 | P=0.475N P=0.750 P=0.502N P=0.519N P=0.504 P=0.487N | |POLY 6 | P=0.472N P=0.724 P=0.501N P=0.543N P=0.493 P=0.492N | |LOGISTIC REGRESSION| P=0.474N P=0.749 (e) (e) P=0.455 (e) | |COCH-ARM / FISHERS | P=0.511N P=0.743N P=0.495N P=0.505N P=0.507 P=0.500N | |ORDER RESTRICTED | P=0.306N (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 | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 21/52 (40%) 15/54 (28%) 17/53 (32%) 16/51 (31%) 14/53 (26%) 11/52 (21%) | |POLY-3 RATE (b) | 21/42.85 15/37.10 17/39.42 16/37.06 14/41.12 11/43.05 | |POLY-3 PERCENT (g) | 49.0% 40.4% 43.1% 43.2% 34.0% 25.6% | |TERMINAL (d) | 11/25 (44%) 10/21 (48%) 13/23 (57%) 8/19 (42%) 9/22 (41%) 6/21 (29%) | |FIRST INCIDENCE | 474 462 626 338 486 638 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.044N* P=0.354N P=0.358N P=0.534N P=0.188N P=0.066N | |POLY 3 | P=0.008N** P=0.288N P=0.374N P=0.380N P=0.115N P=0.017N* | |POLY 1.5 | P=0.013N* P=0.202N P=0.333N P=0.304N P=0.101N P=0.016N* | |POLY 6 | P=0.008N** P=0.415N P=0.446N P=0.495N P=0.145N P=0.025N* | |LOGISTIC REGRESSION| P=0.012N* P=0.225N P=0.264N P=0.316N P=0.095N P=0.016N* | |COCH-ARM / FISHERS | P=0.043N* P=0.122N P=0.247N P=0.227N P=0.095N P=0.027N* | |ORDER RESTRICTED | P=0.011N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 16 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Uterus | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 0/53 (0%) 2/54 (4%) 0/53 (0%) 1/53 (2%) 2/53 (4%) 1/53 (2%) | |POLY-3 RATE (b) | 0/39.55 2/34.61 0/38.75 1/34.16 2/39.00 1/42.66 | |POLY-3 PERCENT (g) | 0.0% 5.8% 0.0% 2.9% 5.1% 2.3% | |TERMINAL (d) | 0/25 (0%) 2/21 (10%) 0/23 (0%) 1/19 (5%) 2/22 (9%) 0/21 (0%) | |FIRST INCIDENCE | --- 731 (T) --- 731 (T) 731 (T) 716 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.421 P=0.200 (e) P=0.445 P=0.210 P=0.492 | |POLY 3 | P=0.489 P=0.208 (e) P=0.471 P=0.233 P=0.515 | |POLY 1.5 | P=0.485 P=0.221 (e) P=0.483 P=0.235 P=0.513 | |POLY 6 | P=0.476 P=0.195 (e) P=0.456 P=0.229 P=0.511 | |LOGISTIC REGRESSION| P=0.443 P=0.200 (e) P=0.445 P=0.210 P=0.501 | |COCH-ARM / FISHERS | P=0.441 P=0.252 (e) P=0.500 P=0.248 P=0.500 | |ORDER RESTRICTED | P=0.246 (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 | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 11/53 (21%) 7/54 (13%) 4/53 (8%) 11/53 (21%) 10/53 (19%) 8/53 (15%) | |POLY-3 RATE (b) | 11/40.11 7/35.74 4/39.04 11/36.29 10/40.43 8/44.05 | |POLY-3 PERCENT (g) | 27.4% 19.6% 10.3% 30.3% 24.7% 18.2% | |TERMINAL (d) | 8/25 (32%) 5/21 (24%) 2/23 (9%) 6/19 (32%) 5/22 (23%) 3/21 (14%) | |FIRST INCIDENCE | 645 526 659 557 590 598 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.531 P=0.361N P=0.064N P=0.314 P=0.589 P=0.400N | |POLY 3 | P=0.404N P=0.296N P=0.045N* P=0.490 P=0.492N P=0.223N | |POLY 1.5 | P=0.452N P=0.257N P=0.048N* P=0.531 P=0.496N P=0.240N | |POLY 6 | P=0.386N P=0.342N P=0.043N* P=0.445 P=0.491N P=0.225N | |LOGISTIC REGRESSION| P=0.439N P=0.359N P=0.045N* P=0.395 P=0.527N P=0.253N | |COCH-ARM / FISHERS | P=0.497 P=0.207N P=0.046N* P=0.594N P=0.500N P=0.307N | |ORDER RESTRICTED | P=0.245N (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 17 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Uterus | | Squamous Cell Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 5/53 (9%) 0/53 (0%) | |POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 0/34.16 5/40.55 0/42.60 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 12.3% 0.0% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- --- --- --- 589 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.300 (e) (e) (e) P=0.035 * (e) | |POLY 3 | P=0.337 (e) (e) (e) P=0.032 * (e) | |POLY 1.5 | P=0.318 (e) (e) (e) P=0.031 * (e) | |POLY 6 | P=0.328 (e) (e) (e) P=0.033 * (e) | |LOGISTIC REGRESSION| P=0.259 (e) (e) (e) P=0.033 * (e) | |COCH-ARM / FISHERS | P=0.247 (e) (e) (e) P=0.028 * (e) | |ORDER RESTRICTED | P=0.033 * (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 | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 0/53 (0%) 0/54 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 0/39.55 0/34.61 0/38.75 0/34.16 2/39.00 0/42.60 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 5.1% 0.0% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 2/22 (9%) 0/21 (0%) | |FIRST INCIDENCE | --- --- --- --- 731 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.446 (e) (e) (e) P=0.210 (e) | |POLY 3 | P=0.544 (e) (e) (e) P=0.233 (e) | |POLY 1.5 | P=0.527 (e) (e) (e) P=0.235 (e) | |POLY 6 | P=0.542 (e) (e) (e) P=0.229 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.210 (e) | |COCH-ARM / FISHERS | P=0.461 (e) (e) (e) P=0.248 (e) | |ORDER RESTRICTED | P=0.183 (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 18 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 0/53 (0%) 1/54 (2%) 1/53 (2%) 0/53 (0%) 1/53 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 0/39.55 1/35.31 1/39.12 0/34.16 1/39.64 2/42.60 | |POLY-3 PERCENT (g) | 0.0% 2.8% 2.6% 0.0% 2.5% 4.7% | |TERMINAL (d) | 0/25 (0%) 0/21 (0%) 0/23 (0%) 0/19 (0%) 0/22 (0%) 2/21 (10%) | |FIRST INCIDENCE | --- 490 626 --- 518 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.170 P=0.491 P=0.484 (e) P=0.505 P=0.200 | |POLY 3 | P=0.172 P=0.477 P=0.498 (e) P=0.500 P=0.254 | |POLY 1.5 | P=0.166 P=0.488 P=0.496 (e) P=0.500 P=0.252 | |POLY 6 | P=0.169 P=0.467 P=0.500 (e) P=0.499 P=0.247 | |LOGISTIC REGRESSION| P=0.138 P=0.536 P=0.500 (e) P=0.504 P=0.200 | |COCH-ARM / FISHERS | P=0.145 P=0.505 P=0.500 (e) P=0.500 P=0.248 | |ORDER RESTRICTED | P=0.107 (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 | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 45/53 (85%) 49/54 (91%) 45/53 (85%) 40/53 (75%) 46/53 (87%) 42/53 (79%) | |POLY-3 RATE (b) | 45/48.82 49/50.46 45/47.09 40/44.36 46/49.52 42/49.59 | |POLY-3 PERCENT (g) | 92.2% 97.1% 95.6% 90.2% 92.9% 84.7% | |TERMINAL (d) | 23/25 (92%) 21/21 (100%) 22/23 (96%) 17/19 (90%) 21/22 (96%) 18/21 (86%) | |FIRST INCIDENCE | 185 241 236 338 141 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.198N P=0.069 P=0.432 P=0.268 P=0.312 P=0.555 | |POLY 3 | P=0.010N* P=0.232 P=0.383 P=0.511N P=0.610 P=0.173N | |POLY 1.5 | P=0.017N* P=0.211 P=0.368 P=0.349N P=0.575 P=0.182N | |POLY 6 | P=0.019N* P=0.301 P=0.440 P=0.657N P=0.619 P=0.217N | |LOGISTIC REGRESSION| P=0.007N** P=0.129 P=0.451 P=0.309N P=0.487 P=0.125N | |COCH-ARM / FISHERS | P=0.178N P=0.266 P=0.607N P=0.165N P=0.500 P=0.307N | |ORDER RESTRICTED | P=0.018N* (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 03 Page 19 Statistical Analysis of Primary Tumors in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 3 NG/KG 10 NG/KG 22 NG/KG 46 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 13/53 (25%) 19/54 (35%) 13/53 (25%) 11/53 (21%) 24/53 (45%) 34/53 (64%) | |POLY-3 RATE (b) | 13/43.94 19/41.93 13/42.97 11/38.84 24/42.50 34/48.63 | |POLY-3 PERCENT (g) | 29.6% 45.3% 30.3% 28.3% 56.5% 69.9% | |TERMINAL (d) | 4/25 (16%) 7/21 (33%) 3/23 (13%) 3/19 (16%) 12/22 (55%) 14/21 (67%) | |FIRST INCIDENCE | 169 200 240 338 518 546 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.090 P=0.533 P=0.549 P=0.022 * P<0.001 ** | |POLY 3 | P<0.001 ** P=0.093 P=0.566 P=0.547N P=0.008 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.121 P=0.554 P=0.493N P=0.010 * P<0.001 ** | |POLY 6 | P<0.001 ** P=0.067 P=0.579 P=0.581 P=0.006 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.211 P=0.572N P=0.355N P=0.019 * P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.160 P=0.589N P=0.408N P=0.020 * 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 | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # # | |----------- | | |OVERALL (a) | 47/53 (89%) 54/54 (100%) 48/53 (91%) 44/53 (83%) 50/53 (94%) 50/53 (94%) | |POLY-3 RATE (b) | 47/50.68 54/54.00 48/49.12 44/46.61 50/51.10 50/51.78 | |POLY-3 PERCENT (g) | 92.7% 100.0% 97.7% 94.4% 97.9% 96.6% | |TERMINAL (d) | 23/25 (92%) 21/21 (100%) 22/23 (96%) 18/19 (95%) 21/22 (96%) 20/21 (95%) | |FIRST INCIDENCE | 169 200 236 338 141 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.436N P=0.037 * P=0.376 P=0.184 P=0.233 P=0.256 | |POLY 3 | P=0.560 P=0.046 * P=0.223 P=0.535 P=0.205 P=0.317 | |POLY 1.5 | P=0.526 P=0.027 * P=0.191 P=0.650 P=0.168 P=0.286 | |POLY 6 | P=0.571 P=0.088 P=0.314 P=0.464 P=0.298 P=0.360 | |LOGISTIC REGRESSION| P=0.387N P=0.014 * P=0.358 P=0.423N P=0.230 P=0.346 | |COCH-ARM / FISHERS | P=0.342 P=0.013 * P=0.500 P=0.289N P=0.244 P=0.244 | |ORDER RESTRICTED | P=0.109 (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).