TDMS Study 96007-01 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB-126) DATE: 10/01/03 EXPERIMENT: 96007 TEST: 01 TIME: 12:19:51 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-75411 ROUTE: GAVAGE NTP C#: 96007D PATHOLOGIST: MISSING CAS: 57465-28-8 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #3/RATS CONTROL VS. GROUPS 3, 4, & 5 REASONS FOR REMOVAL: 25022 Accidently Killed 25018 Dosing Accident 25019 Moribund Sacrifice 25020 Natural Death 25021 Terminal Sacrifice REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 001 0 NG/KG INCLUDE 003 30 NG/KG INCLUDE 004 100 NG/KG INCLUDE 005 175 NG/KG NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB-126) DATE: 10/01/03 EXPERIMENT: 96007 TEST: 01 TIME: 12:19:51 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-75411 ROUTE: GAVAGE NTP C#: 96007D PATHOLOGIST: MISSING CAS: 57465-28-8 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TOXIC EQUIVALENCY FACTOR EVALUATION ( =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Angiectasis Hyperplasia Adrenal Medulla Hyperplasia Blood Vessel: Aorta Mineralization Bone Marrow Hyperplasia Clitoral Gland Inflammation Clitoral Gland: Duct Cyst Kidney Cyst Mineralization Nephropathy Kidney: Pelvis Inflammation Liver Angiectasis Eosinophilic Focus Fatty Change Diffuse Fatty Change Focal Hepatocyte, Multinucleate Inflammation Mixed Cell Focus Necrosis Pigmentation Toxic Hepatopathy Liver: Bile Duct Cyst Hyperplasia Liver: Hepatocyte Degeneration Hypertrophy Liver: Oval Cell Hyperplasia Lung Infiltration Cellular Histiocyte Inflammation Chronic Inflammation Granulomatous Lung: Alveolar Epithelium Hyperplasia Metaplasia Bronchiolar Lymph Node, Mandibular Hyperplasia Lymph Node, Mesenteric Hyperplasia Mammary Gland Cyst Hyperplasia Ovary Atrophy Pancreas Inflammation Chronic Pancreas: Acinus Vacuolization Cytoplasmic Spleen Hematopoietic Cell Proliferation Pigmentation Spleen: Lymphoid Follicle Atrophy Spleen: Red Pulp Atrophy Thymus Atrophy Thyroid Gland: Follicular Cell Hypertrophy Uterus Inflammation Chronic =============================================================== Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/52 (21%) 13/55 (24%) 25/53 (47%) 19/53 (36%) | |POLY-3 RATE (b) | 11/34.50 13/39.17 25/43.24 19/38.60 | |POLY-3 PERCENT (g) | 31.9% 33.2% 57.8% 49.2% | |TERMINAL (d) | 4/15 (27%) 12/25 (48%) 16/26 (62%) 14/22 (64%) | |FIRST INCIDENCE | 541 516 498 658 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.061 P=0.327N P=0.148 P=0.299 | |POLY 3 | P=0.018 * P=0.553 P=0.016 * P=0.092 | |POLY 1.5 | P=0.021 * P=0.519 P=0.009 ** P=0.096 | |POLY 6 | P=0.013 * P=0.594 P=0.028 * P=0.078 | |LOGISTIC REGRESSION| P=0.032 * P=0.541N P=0.019 * P=0.167 | |COCH-ARM / FISHERS | P=0.015 * P=0.470 P=0.004 ** P=0.073 | |ORDER RESTRICTED | P=0.037 * (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 3/55 (5%) 5/53 (9%) 3/53 (6%) | |POLY-3 RATE (b) | 1/31.36 3/38.64 5/41.14 3/38.30 | |POLY-3 PERCENT (g) | 3.2% 7.8% 12.2% 7.8% | |TERMINAL (d) | 1/15 (7%) 2/25 (8%) 3/26 (12%) 0/22 (0%) | |FIRST INCIDENCE | 727 (T) 700 300 592 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.312 P=0.502 P=0.218 P=0.410 | |POLY 3 | P=0.322 P=0.382 P=0.176 P=0.379 | |POLY 1.5 | P=0.299 P=0.356 P=0.148 P=0.357 | |POLY 6 | P=0.341 P=0.424 P=0.214 P=0.405 | |LOGISTIC REGRESSION| P=0.266 P=0.486 P=0.115 P=0.358 | |COCH-ARM / FISHERS | P=0.236 P=0.330 P=0.107 P=0.316 | |ORDER RESTRICTED | P=0.249 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/52 (21%) 14/55 (25%) 10/53 (19%) 14/53 (26%) | |POLY-3 RATE (b) | 11/34.41 14/40.34 10/40.23 14/39.18 | |POLY-3 PERCENT (g) | 32.0% 34.7% 24.9% 35.7% | |TERMINAL (d) | 4/15 (27%) 9/25 (36%) 7/26 (27%) 9/22 (41%) | |FIRST INCIDENCE | 496 516 651 496 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.443N P=0.423N P=0.134N P=0.539N | |POLY 3 | P=0.511 P=0.498 P=0.334N P=0.462 | |POLY 1.5 | P=0.499 P=0.446 P=0.379N P=0.437 | |POLY 6 | P=0.496 P=0.576 P=0.290N P=0.474 | |LOGISTIC REGRESSION| P=0.525N P=0.526 P=0.277N P=0.506 | |COCH-ARM / FISHERS | P=0.405 P=0.384 P=0.480N P=0.344 | |ORDER RESTRICTED | P=0.495 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 23/52 (44%) 21/55 (38%) 27/53 (51%) 25/53 (47%) | |POLY-3 RATE (b) | 23/38.88 21/40.99 27/43.02 25/42.19 | |POLY-3 PERCENT (g) | 59.2% 51.2% 62.8% 59.3% | |TERMINAL (d) | 7/15 (47%) 15/25 (60%) 16/26 (62%) 12/22 (55%) | |FIRST INCIDENCE | 309 434 531 530 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.490N P=0.046N* P=0.181N P=0.289N | |POLY 3 | P=0.351 P=0.305N P=0.455 P=0.590 | |POLY 1.5 | P=0.334 P=0.312N P=0.410 P=0.571 | |POLY 6 | P=0.355 P=0.300N P=0.510 P=0.594 | |LOGISTIC REGRESSION| P=0.420 P=0.200N P=0.576 P=0.508N | |COCH-ARM / FISHERS | P=0.234 P=0.330N P=0.311 P=0.458 | |ORDER RESTRICTED | P=0.453 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 34/52 (65%) 41/55 (75%) 40/53 (75%) 41/53 (77%) | |POLY-3 RATE (b) | 34/39.07 41/45.61 40/45.30 41/44.98 | |POLY-3 PERCENT (g) | 87.0% 89.9% 88.3% 91.2% | |TERMINAL (d) | 15/15 (100%) 22/25 (88%) 24/26 (92%) 22/22 (100%) | |FIRST INCIDENCE | 391 356 498 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.387N P=0.129N P=0.060N P=0.313N | |POLY 3 | P=0.350 P=0.464 P=0.575 P=0.360 | |POLY 1.5 | P=0.307 P=0.290 P=0.381 P=0.278 | |POLY 6 | P=0.303 P=0.606N P=0.556N P=0.462 | |LOGISTIC REGRESSION| P=0.514 P=0.369 P=0.539N P=0.477 | |COCH-ARM / FISHERS | P=0.133 P=0.205 P=0.179 P=0.127 | |ORDER RESTRICTED | P=0.365 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/52 (10%) 3/55 (5%) 5/53 (9%) 2/53 (4%) | |POLY-3 RATE (b) | 5/32.65 3/38.73 5/40.96 2/37.58 | |POLY-3 PERCENT (g) | 15.3% 7.8% 12.2% 5.3% | |TERMINAL (d) | 3/15 (20%) 1/25 (4%) 2/26 (8%) 1/22 (5%) | |FIRST INCIDENCE | 496 681 428 658 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.169N P=0.169N P=0.369N P=0.118N | |POLY 3 | P=0.212N P=0.263N P=0.483N P=0.159N | |POLY 1.5 | P=0.217N P=0.291N P=0.532N P=0.171N | |POLY 6 | P=0.222N P=0.223N P=0.422N P=0.148N | |LOGISTIC REGRESSION| P=0.210N P=0.256N P=0.560N P=0.161N | |COCH-ARM / FISHERS | P=0.256N P=0.327N P=0.617N P=0.211N | |ORDER RESTRICTED | P=0.138N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/55 (0%) 2/53 (4%) 1/53 (2%) | |POLY-3 RATE (b) | 0/31.36 0/38.53 2/39.67 1/37.32 | |POLY-3 PERCENT (g) | 0.0% 0.0% 5.0% 2.7% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/26 (4%) 1/22 (5%) | |FIRST INCIDENCE | --- --- 709 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.201 (e) P=0.368 P=0.576 | |POLY 3 | P=0.198 (e) P=0.292 P=0.535 | |POLY 1.5 | P=0.196 (e) P=0.273 P=0.526 | |POLY 6 | P=0.195 (e) P=0.318 P=0.543 | |LOGISTIC REGRESSION| P=0.189 (e) P=0.341 P=0.576 | |COCH-ARM / FISHERS | P=0.173 (e) P=0.252 P=0.505 | |ORDER RESTRICTED | P=0.215 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/52 (15%) 18/55 (33%) 11/53 (21%) 11/53 (21%) | |POLY-3 RATE (b) | 8/33.72 18/40.38 11/41.48 11/39.17 | |POLY-3 PERCENT (g) | 23.7% 44.6% 26.5% 28.1% | |TERMINAL (d) | 3/15 (20%) 12/25 (48%) 7/26 (27%) 7/22 (32%) | |FIRST INCIDENCE | 496 580 376 496 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.246N P=0.208 P=0.511N P=0.566 | |POLY 3 | P=0.280N P=0.046 * P=0.496 P=0.438 | |POLY 1.5 | P=0.315N P=0.035 * P=0.434 P=0.409 | |POLY 6 | P=0.265N P=0.073 P=0.566 P=0.461 | |LOGISTIC REGRESSION| P=0.313N P=0.066 P=0.445 P=0.438 | |COCH-ARM / FISHERS | P=0.448N P=0.030 * P=0.323 P=0.323 | |ORDER RESTRICTED | P=0.312 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Blood Vessel: Aorta | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 1/55 (2%) 1/53 (2%) 0/53 (0%) | |POLY-3 RATE (b) | 3/32.76 1/39.50 1/40.46 0/37.32 | |POLY-3 PERCENT (g) | 9.2% 2.5% 2.5% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 583 223 376 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.063N P=0.255N P=0.239N P=0.097N | |POLY 3 | P=0.074N P=0.240N P=0.233N P=0.096N | |POLY 1.5 | P=0.073N P=0.259N P=0.255N P=0.100N | |POLY 6 | P=0.081N P=0.218N P=0.213N P=0.093N | |LOGISTIC REGRESSION| P=0.121N P=0.326N P=0.360N P=0.118N | |COCH-ARM / FISHERS | P=0.078N P=0.295N P=0.309N P=0.121N | |ORDER RESTRICTED | P=0.027N* (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 47/53 (89%) 37/55 (67%) 35/53 (66%) 44/53 (83%) | |POLY-3 RATE (b) | 47/52.12 37/50.34 35/50.58 44/52.04 | |POLY-3 PERCENT (g) | 90.2% 73.5% 69.2% 84.6% | |TERMINAL (d) | 10/15 (67%) 14/25 (56%) 12/26 (46%) 16/22 (73%) | |FIRST INCIDENCE | 126 223 188 124 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.175N P=0.004N** P=0.002N** P=0.072N | |POLY 3 | P=0.376N P=0.022N* P=0.006N** P=0.282N | |POLY 1.5 | P=0.388N P=0.016N* P=0.005N** P=0.272N | |POLY 6 | P=0.383N P=0.031N* P=0.008N** P=0.310N | |LOGISTIC REGRESSION| P=0.465 P=0.010N* P=0.020N* P=0.436N | |COCH-ARM / FISHERS | P=0.490N P=0.007N** P=0.005N** P=0.289N | |ORDER RESTRICTED | P=0.041N* (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Brain | | Hydrocephalus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 0/55 (0%) 2/53 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 1/32.36 0/38.53 2/39.86 0/37.32 | |POLY-3 PERCENT (g) | 3.1% 0.0% 5.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 201 --- 678 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.508N P=0.489N P=0.623 P=0.496N | |POLY 3 | P=0.519N P=0.465N P=0.572 P=0.472N | |POLY 1.5 | P=0.516N P=0.478N P=0.546 P=0.479N | |POLY 6 | P=0.539N P=0.447N P=0.605 P=0.464N | |LOGISTIC REGRESSION| P=0.588N P=0.524N P=0.434 P=0.710N | |COCH-ARM / FISHERS | P=0.535N P=0.491N P=0.500 P=0.500N | |ORDER RESTRICTED | P=0.299N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 28/50 (56%) 36/55 (65%) 39/52 (75%) 28/50 (56%) | |POLY-3 RATE (b) | 28/40.18 36/47.35 39/48.96 28/42.13 | |POLY-3 PERCENT (g) | 69.7% 76.0% 79.7% 66.5% | |TERMINAL (d) | 9/14 (64%) 19/25 (76%) 19/26 (73%) 13/22 (59%) | |FIRST INCIDENCE | 222 253 188 436 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.130N P=0.325N P=0.406N P=0.134N | |POLY 3 | P=0.371N P=0.326 P=0.188 P=0.467N | |POLY 1.5 | P=0.381N P=0.274 P=0.121 P=0.476N | |POLY 6 | P=0.381N P=0.413 P=0.286 P=0.464N | |LOGISTIC REGRESSION| P=0.392N P=0.287 P=0.055 P=0.424N | |COCH-ARM / FISHERS | P=0.526 P=0.214 P=0.035 * P=0.580N | |ORDER RESTRICTED | P=0.275N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Clitoral Gland: Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 29/50 (58%) 32/55 (58%) 34/52 (65%) 37/50 (74%) | |POLY-3 RATE (b) | 29/40.97 32/47.78 34/46.12 37/45.50 | |POLY-3 PERCENT (g) | 70.8% 67.0% 73.7% 81.3% | |TERMINAL (d) | 8/14 (57%) 14/25 (56%) 17/26 (65%) 15/22 (68%) | |FIRST INCIDENCE | 126 202 188 436 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.417 P=0.157N P=0.153N P=0.498N | |POLY 3 | P=0.072 P=0.435N P=0.472 P=0.170 | |POLY 1.5 | P=0.052 P=0.497N P=0.402 P=0.117 | |POLY 6 | P=0.110 P=0.377N P=0.557 P=0.260 | |LOGISTIC REGRESSION| P=0.055 P=0.562N P=0.383 P=0.113 | |COCH-ARM / FISHERS | P=0.033 * P=0.571 P=0.287 P=0.069 | |ORDER RESTRICTED | P=0.135 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Esophagus: Muscularis | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 1/55 (2%) 0/53 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 2/30.96 1/39.04 0/39.60 1/37.32 | |POLY-3 PERCENT (g) | 6.5% 2.6% 0.0% 2.7% | |TERMINAL (d) | 1/14 (7%) 0/25 (0%) 0/26 (0%) 1/22 (5%) | |FIRST INCIDENCE | 547 574 --- 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.266N P=0.400N P=0.157N P=0.378N | |POLY 3 | P=0.313N P=0.420N P=0.186N P=0.435N | |POLY 1.5 | P=0.311N P=0.445N P=0.201N P=0.450N | |POLY 6 | P=0.324N P=0.384N P=0.170N P=0.421N | |LOGISTIC REGRESSION| P=0.298N P=0.463N P=0.205N P=0.430N | |COCH-ARM / FISHERS | P=0.321N P=0.479N P=0.243N P=0.493N | |ORDER RESTRICTED | P=0.165N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Eye: Retina | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/55 (0%) 3/53 (6%) 1/53 (2%) | |POLY-3 RATE (b) | 0/30.21 0/38.53 3/39.60 1/37.32 | |POLY-3 PERCENT (g) | 0.0% 0.0% 7.6% 2.7% | |TERMINAL (d) | 0/14 (0%) 0/25 (0%) 3/26 (12%) 1/22 (5%) | |FIRST INCIDENCE | --- --- 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.200 (e) P=0.247 P=0.590 | |POLY 3 | P=0.193 (e) P=0.173 P=0.542 | |POLY 1.5 | P=0.190 (e) P=0.155 P=0.533 | |POLY 6 | P=0.188 (e) P=0.198 P=0.551 | |LOGISTIC REGRESSION| (e) (e) P=0.247 P=0.590 | |COCH-ARM / FISHERS | P=0.162 (e) P=0.129 P=0.510 | |ORDER RESTRICTED | P=0.165 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Harderian Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 3/53 (6%) 6/53 (11%) 6/53 (11%) | |POLY-3 RATE (b) | 2/32.88 3/38.60 6/39.67 6/37.35 | |POLY-3 PERCENT (g) | 6.1% 7.8% 15.1% 16.1% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 5/26 (19%) 5/22 (23%) | |FIRST INCIDENCE | 321 652 709 720 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.106 P=0.643 P=0.315 P=0.260 | |POLY 3 | P=0.079 P=0.573 P=0.199 P=0.173 | |POLY 1.5 | P=0.080 P=0.543 P=0.175 P=0.165 | |POLY 6 | P=0.073 P=0.614 P=0.231 P=0.178 | |LOGISTIC REGRESSION| P=0.086 P=0.500 P=0.180 P=0.178 | |COCH-ARM / FISHERS | P=0.064 P=0.500 P=0.135 P=0.135 | |ORDER RESTRICTED | P=0.155 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/52 (17%) 16/54 (30%) 17/53 (32%) 16/53 (30%) | |POLY-3 RATE (b) | 9/35.59 16/38.84 17/40.82 16/40.33 | |POLY-3 PERCENT (g) | 25.3% 41.2% 41.7% 39.7% | |TERMINAL (d) | 2/15 (13%) 10/24 (42%) 14/26 (54%) 9/22 (41%) | |FIRST INCIDENCE | 201 574 376 448 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.300 P=0.391 P=0.373 P=0.286 | |POLY 3 | P=0.195 P=0.107 P=0.096 P=0.132 | |POLY 1.5 | P=0.177 P=0.096 P=0.082 P=0.120 | |POLY 6 | P=0.201 P=0.139 P=0.115 P=0.144 | |LOGISTIC REGRESSION| P=0.202 P=0.139 P=0.105 P=0.115 | |COCH-ARM / FISHERS | P=0.121 P=0.103 P=0.063 P=0.093 | |ORDER RESTRICTED | P=0.118 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Heart: Epicardium | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 0/54 (0%) 0/53 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 2/32.82 0/37.53 0/39.60 1/38.32 | |POLY-3 PERCENT (g) | 6.1% 0.0% 0.0% 2.6% | |TERMINAL (d) | 0/15 (0%) 0/24 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 126 --- --- 124 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.434N P=0.216N P=0.213N P=0.480N | |POLY 3 | P=0.448N P=0.207N P=0.197N P=0.446N | |POLY 1.5 | P=0.442N P=0.218N P=0.210N P=0.458N | |POLY 6 | P=0.461N P=0.191N P=0.182N P=0.436N | |LOGISTIC REGRESSION| P=0.613 P=0.245N P=0.351N P=0.737 | |COCH-ARM / FISHERS | P=0.443N P=0.238N P=0.243N P=0.493N | |ORDER RESTRICTED | P=0.097N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Intestine Large, Colon | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 1/55 (2%) 2/53 (4%) 1/53 (2%) | |POLY-3 RATE (b) | 0/31.36 1/38.88 2/39.67 1/37.75 | |POLY-3 PERCENT (g) | 0.0% 2.6% 5.0% 2.7% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE | --- 630 709 604 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.360 P=0.573 P=0.368 P=0.539 | |POLY 3 | P=0.376 P=0.543 P=0.292 P=0.537 | |POLY 1.5 | P=0.363 P=0.528 P=0.273 P=0.527 | |POLY 6 | P=0.384 P=0.564 P=0.318 P=0.547 | |LOGISTIC REGRESSION| P=0.345 P=0.522 P=0.341 P=0.506 | |COCH-ARM / FISHERS | P=0.319 P=0.514 P=0.252 P=0.505 | |ORDER RESTRICTED | P=0.274 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Intestine Large, Rectum | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 2/55 (4%) 3/53 (6%) 0/52 (0%) | |POLY-3 RATE (b) | 2/30.87 2/38.53 3/39.60 0/36.94 | |POLY-3 PERCENT (g) | 6.5% 5.2% 7.6% 0.0% | |TERMINAL (d) | 2/15 (13%) 2/25 (8%) 3/26 (12%) 0/22 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.144N P=0.500N P=0.626N P=0.157N | |POLY 3 | P=0.180N P=0.612N P=0.612 P=0.198N | |POLY 1.5 | P=0.187N P=0.638N P=0.577 P=0.209N | |POLY 6 | P=0.181N P=0.574N P=0.652 P=0.189N | |LOGISTIC REGRESSION| P=0.144N P=0.500N P=0.626N (e) | |COCH-ARM / FISHERS | P=0.224N P=0.670N P=0.509 P=0.248N | |ORDER RESTRICTED | P=0.182N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Islets, Pancreatic | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 2/54 (4%) 1/53 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 1/31.36 2/39.02 1/40.16 1/37.75 | |POLY-3 PERCENT (g) | 3.2% 5.1% 2.5% 2.7% | |TERMINAL (d) | 1/15 (7%) 1/25 (4%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 727 (T) 223 555 604 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.423N P=0.628 P=0.674N P=0.695N | |POLY 3 | P=0.424N P=0.576 P=0.703N P=0.719N | |POLY 1.5 | P=0.438N P=0.549 P=0.724N P=0.730N | |POLY 6 | P=0.417N P=0.613 P=0.676N P=0.706N | |LOGISTIC REGRESSION| P=0.508N P=0.501 P=0.740N P=0.727N | |COCH-ARM / FISHERS | P=0.475N P=0.514 P=0.748N P=0.748N | |ORDER RESTRICTED | P=0.558N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Casts Protein | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 3/55 (5%) 1/53 (2%) 6/53 (11%) | |POLY-3 RATE (b) | 4/31.53 3/39.63 1/40.59 6/38.91 | |POLY-3 PERCENT (g) | 12.7% 7.6% 2.5% 15.4% | |TERMINAL (d) | 3/15 (20%) 0/25 (0%) 0/26 (0%) 2/22 (9%) | |FIRST INCIDENCE | 688 516 188 546 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.367 P=0.282N P=0.077N P=0.563 | |POLY 3 | P=0.332 P=0.376N P=0.111N P=0.506 | |POLY 1.5 | P=0.325 P=0.420N P=0.131N P=0.463 | |POLY 6 | P=0.327 P=0.317N P=0.091N P=0.556 | |LOGISTIC REGRESSION| P=0.301 P=0.387N P=0.166N P=0.487 | |COCH-ARM / FISHERS | P=0.281 P=0.479N P=0.181N P=0.371 | |ORDER RESTRICTED | P=0.197 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/55 (0%) 0/53 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.38 0/38.53 0/39.60 2/37.58 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.3% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 1/22 (5%) | |FIRST INCIDENCE | --- --- --- 659 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.049 * (e) (e) P=0.306 | |POLY 3 | P=0.049 * (e) (e) P=0.279 | |POLY 1.5 | P=0.048 * (e) (e) P=0.267 | |POLY 6 | P=0.049 * (e) (e) P=0.291 | |LOGISTIC REGRESSION| P=0.049 * (e) (e) P=0.285 | |COCH-ARM / FISHERS | P=0.045 * (e) (e) P=0.248 | |ORDER RESTRICTED | P=0.047 * (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/55 (0%) 3/53 (6%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.38 0/38.53 3/40.41 0/37.32 | |POLY-3 PERCENT (g) | 0.0% 0.0% 7.4% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- --- 651 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.430 (e) P=0.205 (e) | |POLY 3 | P=0.429 (e) P=0.170 (e) | |POLY 1.5 | P=0.425 (e) P=0.150 (e) | |POLY 6 | P=0.421 (e) P=0.198 (e) | |LOGISTIC REGRESSION| P=0.404 (e) P=0.145 (e) | |COCH-ARM / FISHERS | P=0.381 (e) P=0.121 (e) | |ORDER RESTRICTED | P=0.215 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 2/55 (4%) 1/53 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 2/31.89 2/39.21 1/39.60 1/37.58 | |POLY-3 PERCENT (g) | 6.3% 5.1% 2.5% 2.7% | |TERMINAL (d) | 1/15 (7%) 1/25 (4%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE | 574 498 727 (T) 658 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.239N P=0.572N P=0.353N P=0.398N | |POLY 3 | P=0.272N P=0.618N P=0.425N P=0.443N | |POLY 1.5 | P=0.278N P=0.645N P=0.450N P=0.458N | |POLY 6 | P=0.275N P=0.580N P=0.396N P=0.429N | |LOGISTIC REGRESSION| P=0.276N P=0.658N P=0.418N P=0.453N | |COCH-ARM / FISHERS | P=0.306N P=0.677N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.363N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 32/53 (60%) 39/55 (71%) 44/53 (83%) 44/53 (83%) | |POLY-3 RATE (b) | 32/42.76 39/47.07 44/50.44 44/49.02 | |POLY-3 PERCENT (g) | 74.8% 82.9% 87.2% 89.8% | |TERMINAL (d) | 12/15 (80%) 21/25 (84%) 22/26 (85%) 21/22 (96%) | |FIRST INCIDENCE | 126 328 188 385 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.260 P=0.241N P=0.416N P=0.438 | |POLY 3 | P=0.027 * P=0.230 P=0.085 P=0.033 * | |POLY 1.5 | P=0.014 * P=0.187 P=0.037 * P=0.021 * | |POLY 6 | P=0.040 * P=0.297 P=0.181 P=0.044 * | |LOGISTIC REGRESSION| P=0.011 * P=0.258 P=0.020 * P=0.024 * | |COCH-ARM / FISHERS | P=0.003 ** P=0.171 P=0.008 ** P=0.008 ** | |ORDER RESTRICTED | P=0.024 * (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 32/53 (60%) 29/55 (53%) 38/53 (72%) 35/53 (66%) | |POLY-3 RATE (b) | 32/43.26 29/42.29 38/44.90 35/44.58 | |POLY-3 PERCENT (g) | 74.0% 68.6% 84.6% 78.5% | |TERMINAL (d) | 11/15 (73%) 20/25 (80%) 26/26 (100%) 21/22 (96%) | |FIRST INCIDENCE | 126 350 376 385 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.507N P=0.013N* P=0.111N P=0.218N | |POLY 3 | P=0.134 P=0.366N P=0.131 P=0.387 | |POLY 1.5 | P=0.134 P=0.363N P=0.124 P=0.375 | |POLY 6 | P=0.093 P=0.352N P=0.133 P=0.347 | |LOGISTIC REGRESSION| P=0.260 P=0.178N P=0.309 P=0.472 | |COCH-ARM / FISHERS | P=0.105 P=0.272N P=0.153 P=0.344 | |ORDER RESTRICTED | P=0.150 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Kidney: Pelvis | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/55 (2%) 0/53 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 2/32.37 1/38.53 0/39.60 0/37.32 | |POLY-3 PERCENT (g) | 6.2% 2.6% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 574 727 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.065N P=0.406N P=0.195N P=0.206N | |POLY 3 | P=0.079N P=0.439N P=0.195N P=0.206N | |POLY 1.5 | P=0.080N P=0.458N P=0.208N P=0.213N | |POLY 6 | P=0.082N P=0.413N P=0.181N P=0.202N | |LOGISTIC REGRESSION| P=0.078N P=0.465N P=0.245N P=0.243N | |COCH-ARM / FISHERS | P=0.084N P=0.486N P=0.248N P=0.248N | |ORDER RESTRICTED | P=0.056N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Kidney: Pelvis | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/55 (0%) 0/53 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 2/32.53 0/38.53 0/39.60 0/37.32 | |POLY-3 PERCENT (g) | 6.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 541 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.100N P=0.211N P=0.201N P=0.206N | |POLY 3 | P=0.122N P=0.200N P=0.196N P=0.207N | |POLY 1.5 | P=0.118N P=0.212N P=0.209N P=0.213N | |POLY 6 | P=0.133N P=0.185N P=0.182N P=0.203N | |LOGISTIC REGRESSION| P=0.127N P=0.239N P=0.263N P=0.260N | |COCH-ARM / FISHERS | P=0.115N P=0.238N P=0.248N P=0.248N | |ORDER RESTRICTED | P=0.020N* (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Kidney: Pelvis | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/55 (4%) 2/53 (4%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.38 2/39.16 2/40.08 2/37.84 | |POLY-3 PERCENT (g) | 0.0% 5.1% 5.0% 5.3% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE | --- 524 586 658 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.298 P=0.307 P=0.331 P=0.316 | |POLY 3 | P=0.305 P=0.289 P=0.295 P=0.280 | |POLY 1.5 | P=0.287 P=0.270 P=0.274 P=0.268 | |POLY 6 | P=0.321 P=0.317 P=0.322 P=0.295 | |LOGISTIC REGRESSION| P=0.256 P=0.257 P=0.270 P=0.269 | |COCH-ARM / FISHERS | P=0.235 P=0.257 P=0.248 P=0.248 | |ORDER RESTRICTED | P=0.228 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Kidney: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 2/55 (4%) 8/53 (15%) 4/53 (8%) | |POLY-3 RATE (b) | 4/32.45 2/39.16 8/41.11 4/38.52 | |POLY-3 PERCENT (g) | 12.3% 5.1% 19.5% 10.4% | |TERMINAL (d) | 2/15 (13%) 1/25 (4%) 4/26 (15%) 1/22 (5%) | |FIRST INCIDENCE | 554 524 498 500 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.406 P=0.204N P=0.444 P=0.479N | |POLY 3 | P=0.354 P=0.253N P=0.308 P=0.547N | |POLY 1.5 | P=0.346 P=0.279N P=0.258 P=0.573N | |POLY 6 | P=0.344 P=0.218N P=0.373 P=0.523N | |LOGISTIC REGRESSION| P=0.332 P=0.281N P=0.269 P=0.585N | |COCH-ARM / FISHERS | P=0.282 P=0.322N P=0.179 P=0.642N | |ORDER RESTRICTED | P=0.317 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 8/55 (15%) 4/53 (8%) 1/53 (2%) | |POLY-3 RATE (b) | 3/31.69 8/38.81 4/39.86 1/37.32 | |POLY-3 PERCENT (g) | 9.5% 20.6% 10.0% 2.7% | |TERMINAL (d) | 2/15 (13%) 7/25 (28%) 3/26 (12%) 1/22 (5%) | |FIRST INCIDENCE | 644 652 659 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.032N* P=0.316 P=0.548N P=0.193N | |POLY 3 | P=0.040N* P=0.169 P=0.624 P=0.247N | |POLY 1.5 | P=0.048N* P=0.142 P=0.581 P=0.262N | |POLY 6 | P=0.035N* P=0.216 P=0.636N P=0.235N | |LOGISTIC REGRESSION| P=0.041N* P=0.264 P=0.616N P=0.216N | |COCH-ARM / FISHERS | P=0.082N P=0.113 P=0.500 P=0.309N | |ORDER RESTRICTED | P=0.069N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/53 (13%) 10/55 (18%) 10/53 (19%) 13/53 (25%) | |POLY-3 RATE (b) | 7/32.51 10/39.34 10/40.14 13/39.28 | |POLY-3 PERCENT (g) | 21.5% 25.4% 24.9% 33.1% | |TERMINAL (d) | 3/15 (20%) 7/25 (28%) 8/26 (31%) 9/22 (41%) | |FIRST INCIDENCE | 541 574 651 454 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.217 P=0.529N P=0.489N P=0.322 | |POLY 3 | P=0.170 P=0.457 P=0.476 P=0.201 | |POLY 1.5 | P=0.153 P=0.401 P=0.412 P=0.171 | |POLY 6 | P=0.171 P=0.538 P=0.550 P=0.229 | |LOGISTIC REGRESSION| P=0.160 P=0.538 P=0.589 P=0.207 | |COCH-ARM / FISHERS | P=0.095 P=0.329 P=0.299 P=0.107 | |ORDER RESTRICTED | P=0.217 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/55 (2%) 0/53 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 2/31.38 1/39.30 0/39.60 0/37.32 | |POLY-3 PERCENT (g) | 6.4% 2.5% 0.0% 0.0% | |TERMINAL (d) | 2/15 (13%) 0/25 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 727 (T) 448 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.060N P=0.373N P=0.127N P=0.157N | |POLY 3 | P=0.081N P=0.422N P=0.189N P=0.200N | |POLY 1.5 | P=0.080N P=0.449N P=0.205N P=0.210N | |POLY 6 | P=0.087N P=0.385N P=0.171N P=0.190N | |LOGISTIC REGRESSION| P=0.077N P=0.461N (e) (e) | |COCH-ARM / FISHERS | P=0.084N P=0.486N P=0.248N P=0.248N | |ORDER RESTRICTED | P=0.052N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/53 (21%) 10/55 (18%) 13/53 (25%) 21/53 (40%) | |POLY-3 RATE (b) | 11/34.24 10/39.49 13/42.24 21/43.22 | |POLY-3 PERCENT (g) | 32.1% 25.3% 30.8% 48.6% | |TERMINAL (d) | 5/15 (33%) 6/25 (24%) 5/26 (19%) 7/22 (32%) | |FIRST INCIDENCE | 405 524 509 385 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.040 * P=0.148N P=0.328N P=0.186 | |POLY 3 | P=0.023 * P=0.347N P=0.548N P=0.103 | |POLY 1.5 | P=0.016 * P=0.393N P=0.565 P=0.068 | |POLY 6 | P=0.032 * P=0.285N P=0.452N P=0.165 | |LOGISTIC REGRESSION| P=0.014 * P=0.312N P=0.581 P=0.056 | |COCH-ARM / FISHERS | P=0.007 ** P=0.462N P=0.408 P=0.028 * | |ORDER RESTRICTED | P=0.044 * (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Fatty Change Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 7/55 (13%) 14/53 (26%) 22/53 (42%) | |POLY-3 RATE (b) | 5/33.58 7/40.50 14/43.35 22/41.83 | |POLY-3 PERCENT (g) | 14.9% 17.3% 32.3% 52.6% | |TERMINAL (d) | 2/15 (13%) 2/25 (8%) 6/26 (23%) 11/22 (50%) | |FIRST INCIDENCE | 126 448 376 481 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.614 P=0.142 P=0.005 ** | |POLY 3 | P<0.001 ** P=0.515 P=0.066 P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.462 P=0.042 * P<0.001 ** | |POLY 6 | P<0.001 ** P=0.594 P=0.111 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.403 P=0.020 * P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.407 P=0.020 * P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Fatty Change Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 6/55 (11%) 8/53 (15%) 6/53 (11%) | |POLY-3 RATE (b) | 2/32.02 6/38.55 8/40.14 6/37.58 | |POLY-3 PERCENT (g) | 6.3% 15.6% 19.9% 16.0% | |TERMINAL (d) | 1/15 (7%) 5/25 (20%) 5/26 (19%) 5/22 (23%) | |FIRST INCIDENCE | 519 722 653 660 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.236 P=0.324 P=0.189 P=0.256 | |POLY 3 | P=0.213 P=0.197 P=0.091 P=0.186 | |POLY 1.5 | P=0.197 P=0.174 P=0.073 P=0.172 | |POLY 6 | P=0.218 P=0.235 P=0.120 P=0.198 | |LOGISTIC REGRESSION| P=0.196 P=0.250 P=0.110 P=0.209 | |COCH-ARM / FISHERS | P=0.139 P=0.147 P=0.046 * P=0.135 | |ORDER RESTRICTED | P=0.140 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Hepatocyte, Multinucleate | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/55 (4%) 10/53 (19%) 14/53 (26%) | |POLY-3 RATE (b) | 0/31.38 2/38.53 10/40.61 14/40.28 | |POLY-3 PERCENT (g) | 0.0% 5.2% 24.6% 34.8% | |TERMINAL (d) | 0/15 (0%) 2/25 (8%) 7/26 (27%) 8/22 (36%) | |FIRST INCIDENCE | --- 727 (T) 509 481 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.356 P=0.012 * P<0.001 ** | |POLY 3 | P<0.001 ** P=0.285 P=0.003 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.268 P=0.002 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.310 P=0.006 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.356 P=0.005 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.257 P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 36/53 (68%) 40/55 (73%) 49/53 (92%) 50/53 (94%) | |POLY-3 RATE (b) | 36/42.80 40/46.70 49/50.26 50/50.96 | |POLY-3 PERCENT (g) | 84.1% 85.7% 97.5% 98.1% | |TERMINAL (d) | 15/15 (100%) 21/25 (84%) 25/26 (96%) 22/22 (100%) | |FIRST INCIDENCE | 176 253 188 385 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.136 P=0.082N P=0.334N P=0.405 | |POLY 3 | P<0.001 ** P=0.543 P=0.008 ** P=0.004 ** | |POLY 1.5 | P<0.001 ** P=0.427 P=0.002 ** P<0.001 ** | |POLY 6 | P=0.004 ** P=0.527N P=0.061 P=0.020 * | |LOGISTIC REGRESSION| P<0.001 ** P=0.548 P=0.009 ** P=0.003 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.369 P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P=0.002 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 21/53 (40%) 24/55 (44%) 32/53 (60%) 32/53 (60%) | |POLY-3 RATE (b) | 21/34.34 24/40.37 32/42.94 32/43.91 | |POLY-3 PERCENT (g) | 61.2% 59.5% 74.5% 72.9% | |TERMINAL (d) | 12/15 (80%) 19/25 (76%) 22/26 (85%) 19/22 (86%) | |FIRST INCIDENCE | 541 546 541 385 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.081 P=0.087N P=0.449N P=0.349 | |POLY 3 | P=0.057 P=0.537N P=0.131 P=0.170 | |POLY 1.5 | P=0.033 * P=0.553 P=0.071 P=0.099 | |POLY 6 | P=0.073 P=0.398N P=0.257 P=0.261 | |LOGISTIC REGRESSION| P=0.024 * P=0.313N P=0.257 P=0.104 | |COCH-ARM / FISHERS | P=0.007 ** P=0.410 P=0.026 * P=0.026 * | |ORDER RESTRICTED | P=0.136 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 2/55 (4%) 5/53 (9%) 8/53 (15%) | |POLY-3 RATE (b) | 4/34.03 2/39.44 5/42.49 8/41.14 | |POLY-3 PERCENT (g) | 11.8% 5.1% 11.8% 19.5% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 176 356 300 481 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.078 P=0.242N P=0.624 P=0.294 | |POLY 3 | P=0.067 P=0.269N P=0.637 P=0.278 | |POLY 1.5 | P=0.060 P=0.291N P=0.589 P=0.243 | |POLY 6 | P=0.072 P=0.240N P=0.583N P=0.320 | |LOGISTIC REGRESSION| P=0.017 * P=0.373N P=0.320 P=0.101 | |COCH-ARM / FISHERS | P=0.043 * P=0.322N P=0.500 P=0.179 | |ORDER RESTRICTED | P=0.109 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 11/55 (20%) 41/53 (77%) 39/53 (74%) | |POLY-3 RATE (b) | 1/32.06 11/39.46 41/47.21 39/44.38 | |POLY-3 PERCENT (g) | 3.1% 27.9% 86.9% 87.9% | |TERMINAL (d) | 0/15 (0%) 7/25 (28%) 23/26 (89%) 21/22 (96%) | |FIRST INCIDENCE | 496 572 328 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.024 * P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.005 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.004 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.009 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.008 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Toxic Hepatopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 6/55 (11%) 22/53 (42%) 27/53 (51%) | |POLY-3 RATE (b) | 0/31.38 6/38.95 22/41.68 27/41.02 | |POLY-3 PERCENT (g) | 0.0% 15.4% 52.8% 65.8% | |TERMINAL (d) | 0/15 (0%) 3/25 (12%) 15/26 (58%) 18/22 (82%) | |FIRST INCIDENCE | --- 652 328 454 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.068 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.029 * P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.023 * P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.040 * P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.042 * P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.015 * P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 6/55 (11%) 0/53 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 3/31.38 6/38.56 0/39.60 2/37.58 | |POLY-3 PERCENT (g) | 9.6% 15.6% 0.0% 5.3% | |TERMINAL (d) | 3/15 (20%) 5/25 (20%) 0/26 (0%) 1/22 (5%) | |FIRST INCIDENCE | 727 (T) 720 --- 659 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.055N P=0.545 P=0.042N* P=0.343N | |POLY 3 | P=0.068N P=0.350 P=0.082N P=0.418N | |POLY 1.5 | P=0.078N P=0.311 P=0.094N P=0.441N | |POLY 6 | P=0.059N P=0.412 P=0.069N P=0.394N | |LOGISTIC REGRESSION| P=0.063N P=0.568 (e) P=0.373N | |COCH-ARM / FISHERS | P=0.111N P=0.263 P=0.121N P=0.500N | |ORDER RESTRICTED | P=0.087N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 4/55 (7%) 3/53 (6%) 2/53 (4%) | |POLY-3 RATE (b) | 4/32.23 4/38.64 3/39.75 2/38.02 | |POLY-3 PERCENT (g) | 12.4% 10.4% 7.6% 5.3% | |TERMINAL (d) | 3/15 (20%) 3/25 (12%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE | 391 700 709 600 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.144N P=0.382N P=0.253N P=0.223N | |POLY 3 | P=0.172N P=0.541N P=0.386N P=0.262N | |POLY 1.5 | P=0.183N P=0.577N P=0.426N P=0.283N | |POLY 6 | P=0.167N P=0.485N P=0.338N P=0.239N | |LOGISTIC REGRESSION| P=0.168N P=0.512N P=0.378N P=0.289N | |COCH-ARM / FISHERS | P=0.225N P=0.621N P=0.500N P=0.339N | |ORDER RESTRICTED | P=0.243N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 7/55 (13%) 7/53 (13%) 13/53 (25%) | |POLY-3 RATE (b) | 3/32.67 7/39.97 7/39.86 13/41.26 | |POLY-3 PERCENT (g) | 9.2% 17.5% 17.6% 31.5% | |TERMINAL (d) | 1/15 (7%) 4/25 (16%) 6/26 (23%) 5/22 (23%) | |FIRST INCIDENCE | 496 434 659 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.018 * P=0.337 P=0.392 P=0.036 * | |POLY 3 | P=0.013 * P=0.248 P=0.246 P=0.019 * | |POLY 1.5 | P=0.010 * P=0.215 P=0.215 P=0.013 * | |POLY 6 | P=0.016 * P=0.298 P=0.288 P=0.027 * | |LOGISTIC REGRESSION| P=0.008 ** P=0.205 P=0.264 P=0.009 ** | |COCH-ARM / FISHERS | P=0.005 ** P=0.176 P=0.160 P=0.006 ** | |ORDER RESTRICTED | P=0.011 * (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 24 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 1/55 (2%) 1/53 (2%) 0/53 (0%) | |POLY-3 RATE (b) | 3/33.04 1/38.64 1/40.21 0/37.32 | |POLY-3 PERCENT (g) | 9.1% 2.6% 2.5% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 354 700 533 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.061N P=0.210N P=0.233N P=0.094N | |POLY 3 | P=0.072N P=0.250N P=0.238N P=0.097N | |POLY 1.5 | P=0.071N P=0.267N P=0.260N P=0.102N | |POLY 6 | P=0.077N P=0.224N P=0.213N P=0.093N | |LOGISTIC REGRESSION| P=0.091N P=0.302N P=0.375N P=0.151N | |COCH-ARM / FISHERS | P=0.078N P=0.295N P=0.309N P=0.121N | |ORDER RESTRICTED | P=0.027N* (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 23/55 (42%) 32/53 (60%) 36/53 (68%) | |POLY-3 RATE (b) | 0/31.38 23/43.50 32/45.22 36/46.82 | |POLY-3 PERCENT (g) | 0.0% 52.9% 70.8% 76.9% | |TERMINAL (d) | 0/15 (0%) 10/25 (40%) 18/26 (69%) 17/22 (77%) | |FIRST INCIDENCE | --- 448 188 385 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 25 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Oval Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 1/55 (2%) 6/53 (11%) 7/53 (13%) | |POLY-3 RATE (b) | 0/31.38 1/38.56 6/39.60 7/37.32 | |POLY-3 PERCENT (g) | 0.0% 2.6% 15.2% 18.8% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 6/26 (23%) 7/22 (32%) | |FIRST INCIDENCE | --- 720 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.624 P=0.062 P=0.024 * | |POLY 3 | P<0.001 ** P=0.541 P=0.031 * P=0.013 * | |POLY 1.5 | P<0.001 ** P=0.527 P=0.025 * P=0.012 * | |POLY 6 | P<0.001 ** P=0.561 P=0.041 * P=0.015 * | |LOGISTIC REGRESSION| P<0.001 ** P=0.596 P=0.062 P=0.024 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.509 P=0.013 * P=0.006 ** | |ORDER RESTRICTED | P=0.006 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 41/53 (77%) 49/55 (89%) 45/53 (85%) 48/53 (91%) | |POLY-3 RATE (b) | 41/47.06 49/51.17 45/47.89 48/49.78 | |POLY-3 PERCENT (g) | 87.1% 95.8% 94.0% 96.4% | |TERMINAL (d) | 12/15 (80%) 23/25 (92%) 26/26 (100%) 21/22 (96%) | |FIRST INCIDENCE | 201 253 328 385 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.315N P=0.201N P=0.049N* P=0.335N | |POLY 3 | P=0.088 P=0.099 P=0.185 P=0.069 | |POLY 1.5 | P=0.091 P=0.062 P=0.192 P=0.058 | |POLY 6 | P=0.088 P=0.182 P=0.187 P=0.097 | |LOGISTIC REGRESSION| P=0.308 P=0.128 P=0.479 P=0.144 | |COCH-ARM / FISHERS | P=0.094 P=0.084 P=0.229 P=0.055 | |ORDER RESTRICTED | P=0.026 * (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 26 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 3/55 (5%) 0/53 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 5/32.66 3/39.74 0/39.60 1/37.78 | |POLY-3 PERCENT (g) | 15.3% 7.6% 0.0% 2.7% | |TERMINAL (d) | 2/15 (13%) 0/25 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 309 356 --- 592 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.017N* P=0.179N P=0.010N* P=0.057N | |POLY 3 | P=0.022N* P=0.252N P=0.017N* P=0.069N | |POLY 1.5 | P=0.022N* P=0.286N P=0.021N* P=0.077N | |POLY 6 | P=0.023N* P=0.207N P=0.013N* P=0.061N | |LOGISTIC REGRESSION| P=0.027N* P=0.321N P=0.026N* P=0.088N | |COCH-ARM / FISHERS | P=0.027N* P=0.337N P=0.028N* P=0.103N | |ORDER RESTRICTED | P=0.010N* (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 0/55 (0%) 2/53 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 3/32.04 0/38.53 2/39.67 0/37.32 | |POLY-3 PERCENT (g) | 9.4% 0.0% 5.0% 0.0% | |TERMINAL (d) | 1/15 (7%) 0/25 (0%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE | 611 --- 709 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.129N P=0.066N P=0.300N P=0.085N | |POLY 3 | P=0.168N P=0.088N P=0.403N P=0.092N | |POLY 1.5 | P=0.162N P=0.097N P=0.435N P=0.098N | |POLY 6 | P=0.185N P=0.076N P=0.368N P=0.088N | |LOGISTIC REGRESSION| P=0.138N P=0.088N P=0.374N P=0.092N | |COCH-ARM / FISHERS | P=0.171N P=0.115N P=0.500N P=0.121N | |ORDER RESTRICTED | P=0.025N* (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 27 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 0/55 (0%) 1/53 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 1/31.53 0/38.53 1/39.60 2/37.32 | |POLY-3 PERCENT (g) | 3.2% 0.0% 2.5% 5.4% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/26 (4%) 2/22 (9%) | |FIRST INCIDENCE | 688 --- 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.245 P=0.405N P=0.642N P=0.616 | |POLY 3 | P=0.221 P=0.460N P=0.708N P=0.559 | |POLY 1.5 | P=0.223 P=0.474N P=0.727N P=0.543 | |POLY 6 | P=0.213 P=0.441N P=0.685N P=0.572 | |LOGISTIC REGRESSION| P=0.232 P=0.448N P=0.677N P=0.598 | |COCH-ARM / FISHERS | P=0.207 P=0.491N P=0.752N P=0.500 | |ORDER RESTRICTED | P=0.268 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/55 (4%) 0/53 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.38 2/38.67 0/39.60 0/37.32 | |POLY-3 PERCENT (g) | 0.0% 5.2% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- 700 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.245N P=0.374 (e) (e) | |POLY 3 | P=0.225N P=0.286 (e) (e) | |POLY 1.5 | P=0.245N P=0.268 (e) (e) | |POLY 6 | P=0.205N P=0.312 (e) (e) | |LOGISTIC REGRESSION| P=0.250N P=0.322 (e) (e) | |COCH-ARM / FISHERS | P=0.284N P=0.257 (e) (e) | |ORDER RESTRICTED | P=0.258N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 28 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/53 (23%) 1/55 (2%) 0/53 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 12/32.58 1/38.75 0/39.60 1/37.32 | |POLY-3 PERCENT (g) | 36.8% 2.6% 0.0% 2.7% | |TERMINAL (d) | 7/15 (47%) 0/25 (0%) 0/26 (0%) 1/22 (5%) | |FIRST INCIDENCE | 600 671 --- 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 3 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Metaplasia Bronchiolar | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 29/55 (53%) 34/53 (64%) 41/53 (77%) | |POLY-3 RATE (b) | 0/31.38 29/41.27 34/43.69 41/45.19 | |POLY-3 PERCENT (g) | 0.0% 70.3% 77.8% 90.7% | |TERMINAL (d) | 0/15 (0%) 19/25 (76%) 22/26 (85%) 21/22 (96%) | |FIRST INCIDENCE | --- 516 541 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 29 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lung: Serosa | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/55 (0%) 2/53 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.38 0/38.53 2/39.88 0/37.32 | |POLY-3 PERCENT (g) | 0.0% 0.0% 5.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE | --- --- 651 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.502 (e) P=0.358 (e) | |POLY 3 | P=0.498 (e) P=0.294 (e) | |POLY 1.5 | P=0.495 (e) P=0.273 (e) | |POLY 6 | P=0.493 (e) P=0.320 (e) | |LOGISTIC REGRESSION| P=0.483 (e) P=0.300 (e) | |COCH-ARM / FISHERS | P=0.454 (e) P=0.248 (e) | |ORDER RESTRICTED | P=0.296 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lung: Serosa | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/55 (0%) 0/53 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 2/32.84 0/38.53 0/39.60 1/38.32 | |POLY-3 PERCENT (g) | 6.1% 0.0% 0.0% 2.6% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 126 --- --- 124 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.436N P=0.218N P=0.215N P=0.482N | |POLY 3 | P=0.459N P=0.202N P=0.197N P=0.446N | |POLY 1.5 | P=0.451N P=0.214N P=0.211N P=0.459N | |POLY 6 | P=0.473N P=0.186N P=0.182N P=0.436N | |LOGISTIC REGRESSION| P=0.583 P=0.267N P=0.371N P=0.703 | |COCH-ARM / FISHERS | P=0.449N P=0.238N P=0.248N P=0.500N | |ORDER RESTRICTED | P=0.097N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 30 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 1/53 (2%) 4/51 (8%) 4/51 (8%) | |POLY-3 RATE (b) | 1/31.47 1/37.64 4/38.08 4/36.51 | |POLY-3 PERCENT (g) | 3.2% 2.7% 10.5% 11.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 4/25 (16%) 4/22 (18%) | |FIRST INCIDENCE | 660 722 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.079 P=0.658N P=0.344 P=0.293 | |POLY 3 | P=0.068 P=0.720N P=0.240 P=0.224 | |POLY 1.5 | P=0.067 P=0.736N P=0.215 P=0.210 | |POLY 6 | P=0.065 P=0.695N P=0.272 P=0.237 | |LOGISTIC REGRESSION| P=0.066 P=0.709N P=0.309 P=0.264 | |COCH-ARM / FISHERS | P=0.052 P=0.748N P=0.175 P=0.175 | |ORDER RESTRICTED | P=0.158 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 18/52 (35%) 24/53 (45%) 31/51 (61%) 21/51 (41%) | |POLY-3 RATE (b) | 18/36.75 24/45.45 31/41.45 21/38.38 | |POLY-3 PERCENT (g) | 49.0% 52.8% 74.8% 54.7% | |TERMINAL (d) | 8/15 (53%) 9/25 (36%) 21/25 (84%) 16/22 (73%) | |FIRST INCIDENCE | 222 202 531 496 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.457N P=0.485N P=0.366 P=0.347N | |POLY 3 | P=0.170 P=0.450 P=0.010 * P=0.388 | |POLY 1.5 | P=0.228 P=0.328 P=0.007 ** P=0.389 | |POLY 6 | P=0.096 P=0.571N P=0.017 * P=0.369 | |LOGISTIC REGRESSION| P=0.391 P=0.205 P=0.034 * P=0.544 | |COCH-ARM / FISHERS | P=0.224 P=0.180 P=0.007 ** P=0.315 | |ORDER RESTRICTED | P=0.108 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 31 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 3/54 (6%) 0/52 (0%) 1/52 (2%) | |POLY-3 RATE (b) | 2/31.83 3/39.51 0/38.60 1/36.90 | |POLY-3 PERCENT (g) | 6.3% 7.6% 0.0% 2.7% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 0/25 (0%) 0/21 (0%) | |FIRST INCIDENCE | 618 498 --- 546 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.140N P=0.642 P=0.150N P=0.427N | |POLY 3 | P=0.146N P=0.598 P=0.196N P=0.448N | |POLY 1.5 | P=0.153N P=0.562 P=0.210N P=0.462N | |POLY 6 | P=0.144N P=0.644 P=0.181N P=0.437N | |LOGISTIC REGRESSION| P=0.173N P=0.539 P=0.200N P=0.481N | |COCH-ARM / FISHERS | P=0.175N P=0.518 P=0.248N P=0.500N | |ORDER RESTRICTED | P=0.197N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/52 (6%) 0/54 (0%) 0/52 (0%) 0/52 (0%) | |POLY-3 RATE (b) | 3/33.26 0/38.32 0/38.60 0/36.32 | |POLY-3 PERCENT (g) | 9.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/25 (0%) 0/21 (0%) | |FIRST INCIDENCE | 222 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.043N* P=0.095N P=0.093N P=0.102N | |POLY 3 | P=0.052N P=0.094N P=0.093N P=0.102N | |POLY 1.5 | P=0.049N* P=0.102N P=0.102N P=0.106N | |POLY 6 | P=0.059N P=0.083N P=0.084N P=0.100N | |LOGISTIC REGRESSION| P=0.070N P=0.130N P=0.171N P=0.172N | |COCH-ARM / FISHERS | P=0.051N P=0.115N P=0.121N P=0.121N | |ORDER RESTRICTED | P=0.006N** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 32 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 0/6 (0%) 0/6 (0%) 2/6 (33%) | |POLY-3 RATE (b) | 0/0.63 0/3.24 0/3.60 2/4.37 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 45.8% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 0/2 (0%) 0/1 (0%) | |FIRST INCIDENCE | --- --- --- 496 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.056 (e) (e) P=0.309 | |POLY 3 | P=0.080 (e) (e) P=0.682 | |POLY 1.5 | P=0.074 (e) (e) P=0.636 | |POLY 6 | P=0.099 (e) (e) P=0.740 | |LOGISTIC REGRESSION| P=0.067 (e) (e) P=0.581 | |COCH-ARM / FISHERS | P=0.066 (e) (e) P=0.536 | |ORDER RESTRICTED | P=0.501 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 2/6 (33%) 3/6 (50%) 0/6 (0%) | |POLY-3 RATE (b) | 0/0.63 2/3.86 3/4.04 0/3.43 | |POLY-3 PERCENT (g) | 0.0% 51.8% 74.3% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 2/2 (100%) 0/1 (0%) | |FIRST INCIDENCE | --- 630 602 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.360N P=0.331 P=0.581 (e) | |POLY 3 | P=0.191N P=0.673 P=0.593 (e) | |POLY 1.5 | P=0.177N P=0.618 P=0.510 (e) | |POLY 6 | P=0.281N P=0.742 P=0.784 (e) | |LOGISTIC REGRESSION| P=0.199N P=0.662 P=0.527 (e) | |COCH-ARM / FISHERS | P=0.314N P=0.536 P=0.357 (e) | |ORDER RESTRICTED | P=0.493N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 33 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 0/6 (0%) 2/6 (33%) 1/6 (17%) | |POLY-3 RATE (b) | 0/0.63 0/3.24 2/4.04 1/3.97 | |POLY-3 PERCENT (g) | 0.0% 0.0% 49.6% 25.2% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 1/2 (50%) 0/1 (0%) | |FIRST INCIDENCE | --- --- 602 559 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.235 (e) P=0.581 P=0.543 | |POLY 3 | P=0.429 (e) P=0.677 P=0.796 | |POLY 1.5 | P=0.393 (e) P=0.629 P=0.775 | |POLY 6 | P=0.519 (e) P=0.743 P=0.824 | |LOGISTIC REGRESSION| P=0.311 (e) P=0.709 P=0.783 | |COCH-ARM / FISHERS | P=0.269 (e) P=0.536 P=0.750 | |ORDER RESTRICTED | P=0.587 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/52 (15%) 3/55 (5%) 1/53 (2%) 4/53 (8%) | |POLY-3 RATE (b) | 8/33.57 3/39.34 1/40.40 4/37.83 | |POLY-3 PERCENT (g) | 23.8% 7.6% 2.5% 10.6% | |TERMINAL (d) | 3/15 (20%) 1/25 (4%) 0/26 (0%) 3/22 (14%) | |FIRST INCIDENCE | 405 524 428 576 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.082N P=0.031N* P=0.005N** P=0.077N | |POLY 3 | P=0.111N P=0.052N P=0.006N** P=0.116N | |POLY 1.5 | P=0.111N P=0.064N P=0.008N** P=0.128N | |POLY 6 | P=0.118N P=0.038N* P=0.004N** P=0.108N | |LOGISTIC REGRESSION| P=0.112N P=0.066N P=0.014N* P=0.117N | |COCH-ARM / FISHERS | P=0.131N P=0.084N P=0.014N* P=0.170N | |ORDER RESTRICTED | P=0.012N* (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 34 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 32/52 (62%) 33/55 (60%) 30/53 (57%) 29/53 (55%) | |POLY-3 RATE (b) | 32/43.06 33/45.84 30/46.24 29/43.63 | |POLY-3 PERCENT (g) | 74.3% 72.0% 64.9% 66.5% | |TERMINAL (d) | 11/15 (73%) 15/25 (60%) 13/26 (50%) 15/22 (68%) | |FIRST INCIDENCE | 126 82 328 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.082N P=0.082N P=0.031N* P=0.063N | |POLY 3 | P=0.181N P=0.497N P=0.219N P=0.269N | |POLY 1.5 | P=0.189N P=0.540N P=0.295N P=0.277N | |POLY 6 | P=0.195N P=0.374N P=0.127N P=0.267N | |LOGISTIC REGRESSION| P=0.146N P=0.450N P=0.294N P=0.216N | |COCH-ARM / FISHERS | P=0.240N P=0.514N P=0.376N P=0.305N | |ORDER RESTRICTED | P=0.287N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 0/55 (0%) 0/53 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 1/31.36 0/38.53 0/39.60 2/37.74 | |POLY-3 PERCENT (g) | 3.2% 0.0% 0.0% 5.3% | |TERMINAL (d) | 1/15 (7%) 0/25 (0%) 0/26 (0%) 1/22 (5%) | |FIRST INCIDENCE | 727 (T) --- --- 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.265 P=0.398N P=0.390N P=0.607 | |POLY 3 | P=0.240 P=0.459N P=0.454N P=0.564 | |POLY 1.5 | P=0.242 P=0.472N P=0.469N P=0.547 | |POLY 6 | P=0.231 P=0.439N P=0.435N P=0.583 | |LOGISTIC REGRESSION| P=0.256 (e) (e) P=0.572 | |COCH-ARM / FISHERS | P=0.234 P=0.486N P=0.495N P=0.507 | |ORDER RESTRICTED | P=0.167 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 35 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 2/55 (4%) 0/53 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 2/31.43 2/39.32 0/39.60 1/37.83 | |POLY-3 PERCENT (g) | 6.4% 5.1% 0.0% 2.6% | |TERMINAL (d) | 1/15 (7%) 1/25 (4%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 709 434 --- 576 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.183N P=0.535N P=0.129N P=0.395N | |POLY 3 | P=0.210N P=0.611N P=0.189N P=0.435N | |POLY 1.5 | P=0.215N P=0.640N P=0.204N P=0.453N | |POLY 6 | P=0.208N P=0.570N P=0.172N P=0.418N | |LOGISTIC REGRESSION| P=0.219N P=0.643N P=0.141N P=0.439N | |COCH-ARM / FISHERS | P=0.233N P=0.670N P=0.243N P=0.493N | |ORDER RESTRICTED | P=0.208N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Mesentery: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/1 (0%) 0/0 (0%) 2/4 (50%) 2/2 (100%) | |POLY-3 RATE (b) | 0/0.16 0/0.00 2/3.52 2/2.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 56.8% 100.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 2/3 (67%) 2/2 (100%) | |FIRST INCIDENCE | --- --- 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.581 (e) P=1.000 P=1.000 | |POLY 3 | (e) (e) P=0.800 P=0.333 | |POLY 1.5 | (e) (e) P=0.731 P=0.333 | |POLY 6 | (e) (e) P=0.843 P=0.333 | |LOGISTIC REGRESSION| (e) (e) P=1.000 P=1.000 | |COCH-ARM / FISHERS | P=0.120 (e) P=0.600 P=0.333 | |ORDER RESTRICTED | (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 36 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Nose: Respiratory Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/54 (0%) 1/52 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 2/32.23 0/37.53 1/39.58 1/37.32 | |POLY-3 PERCENT (g) | 6.2% 0.0% 2.5% 2.7% | |TERMINAL (d) | 1/15 (7%) 0/24 (0%) 0/26 (0%) 1/22 (5%) | |FIRST INCIDENCE | 391 --- 709 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.461N P=0.185N P=0.365N P=0.395N | |POLY 3 | P=0.521N P=0.204N P=0.429N P=0.449N | |POLY 1.5 | P=0.516N P=0.216N P=0.455N P=0.461N | |POLY 6 | P=0.540N P=0.186N P=0.398N P=0.437N | |LOGISTIC REGRESSION| P=0.506N P=0.240N P=0.501N P=0.484N | |COCH-ARM / FISHERS | P=0.526N P=0.243N P=0.507N P=0.500N | |ORDER RESTRICTED | P=0.212N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Nose: Turbinate | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/54 (0%) 1/52 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 2/31.81 0/37.53 1/39.51 1/37.32 | |POLY-3 PERCENT (g) | 6.3% 0.0% 2.5% 2.7% | |TERMINAL (d) | 1/15 (7%) 0/24 (0%) 1/26 (4%) 1/22 (5%) | |FIRST INCIDENCE | 603 --- 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.458N P=0.165N P=0.344N P=0.393N | |POLY 3 | P=0.522N P=0.201N P=0.425N P=0.444N | |POLY 1.5 | P=0.517N P=0.214N P=0.452N P=0.458N | |POLY 6 | P=0.542N P=0.184N P=0.396N P=0.433N | |LOGISTIC REGRESSION| P=0.479N P=0.201N P=0.405N P=0.429N | |COCH-ARM / FISHERS | P=0.526N P=0.243N P=0.507N P=0.500N | |ORDER RESTRICTED | P=0.209N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 37 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Oral Mucosa: Gingival | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/1 (100%) 0/1 (0%) 2/3 (67%) 2/4 (50%) | |POLY-3 RATE (b) | 1/1.00 0/0.82 2/2.72 2/4.00 | |POLY-3 PERCENT (g) | 100.0% 0.0% 73.6% 50.0% | |TERMINAL (d) | 1/1 (100%) 0/0 (0%) 0/0 (0%) 1/3 (33%) | |FIRST INCIDENCE | 727 (T) --- 688 658 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.478 P=1.000 P=0.377 P=0.729N | |POLY 3 | P=0.485N P=1.000 P=0.786N P=0.577N | |POLY 1.5 | P=0.520N P=1.000 P=0.737N P=0.577N | |POLY 6 | P=0.421N P=1.000 P=0.885N P=0.577N | |LOGISTIC REGRESSION| P=0.555N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.565N P=0.500N P=0.750N P=0.600N | |ORDER RESTRICTED | P=0.419N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Ovary | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 45/52 (87%) 49/54 (91%) 46/53 (87%) 45/52 (87%) | |POLY-3 RATE (b) | 45/46.65 49/52.02 46/50.50 45/49.66 | |POLY-3 PERCENT (g) | 96.5% 94.2% 91.1% 90.6% | |TERMINAL (d) | 14/15 (93%) 22/25 (88%) 23/26 (89%) 19/22 (86%) | |FIRST INCIDENCE | 126 223 188 124 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.104N P=0.075N P=0.020N* P=0.090N | |POLY 3 | P=0.134N P=0.477N P=0.234N P=0.204N | |POLY 1.5 | P=0.145N P=0.654N P=0.314N P=0.271N | |POLY 6 | P=0.174N P=0.376N P=0.217N P=0.218N | |LOGISTIC REGRESSION| P=0.249N P=0.447 P=0.394N P=0.388N | |COCH-ARM / FISHERS | P=0.422N P=0.354 P=0.598 P=0.613N | |ORDER RESTRICTED | P=0.186N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 38 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/52 (23%) 17/54 (31%) 17/53 (32%) 15/52 (29%) | |POLY-3 RATE (b) | 12/33.36 17/41.28 17/40.57 15/38.87 | |POLY-3 PERCENT (g) | 36.0% 41.2% 41.9% 38.6% | |TERMINAL (d) | 7/15 (47%) 10/25 (40%) 15/26 (58%) 10/22 (46%) | |FIRST INCIDENCE | 547 356 541 496 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.433N P=0.505N P=0.411N P=0.481N | |POLY 3 | P=0.506 P=0.411 P=0.387 P=0.506 | |POLY 1.5 | P=0.483 P=0.321 P=0.318 P=0.453 | |POLY 6 | P=0.490 P=0.545 P=0.469 P=0.553 | |LOGISTIC REGRESSION| P=0.531 P=0.379 P=0.549 P=0.547 | |COCH-ARM / FISHERS | P=0.354 P=0.226 P=0.208 P=0.328 | |ORDER RESTRICTED | P=0.542 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/51 (10%) 1/55 (2%) 3/53 (6%) 4/53 (8%) | |POLY-3 RATE (b) | 5/32.80 1/38.53 3/40.81 4/38.15 | |POLY-3 PERCENT (g) | 15.2% 2.6% 7.4% 10.5% | |TERMINAL (d) | 3/15 (20%) 1/25 (4%) 1/26 (4%) 3/22 (14%) | |FIRST INCIDENCE | 391 727 (T) 300 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.525N P=0.041N* P=0.182N P=0.315N | |POLY 3 | P=0.540 P=0.066N P=0.242N P=0.404N | |POLY 1.5 | P=0.540 P=0.075N P=0.275N P=0.424N | |POLY 6 | P=0.524 P=0.053N P=0.203N P=0.385N | |LOGISTIC REGRESSION| P=0.515 P=0.075N P=0.347N P=0.439N | |COCH-ARM / FISHERS | P=0.504 P=0.086N P=0.336N P=0.475N | |ORDER RESTRICTED | P=0.170N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 39 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/51 (10%) 3/55 (5%) 2/53 (4%) 7/53 (13%) | |POLY-3 RATE (b) | 5/31.43 3/38.53 2/40.53 7/38.15 | |POLY-3 PERCENT (g) | 15.9% 7.8% 4.9% 18.4% | |TERMINAL (d) | 4/15 (27%) 3/25 (12%) 1/26 (4%) 6/22 (27%) | |FIRST INCIDENCE | 705 727 (T) 300 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.355 P=0.120N P=0.072N P=0.612N | |POLY 3 | P=0.297 P=0.247N P=0.124N P=0.520 | |POLY 1.5 | P=0.291 P=0.280N P=0.151N P=0.484 | |POLY 6 | P=0.289 P=0.201N P=0.097N P=0.558 | |LOGISTIC REGRESSION| P=0.307 P=0.109N P=0.145N P=0.546 | |COCH-ARM / FISHERS | P=0.254 P=0.316N P=0.203N P=0.408 | |ORDER RESTRICTED | P=0.186 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/55 (0%) 1/53 (2%) 4/53 (8%) | |POLY-3 RATE (b) | 0/31.35 0/38.53 1/39.60 4/39.05 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.5% 10.2% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE | --- --- 727 (T) 595 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.007 ** (e) P=0.610 P=0.092 | |POLY 3 | P=0.006 ** (e) P=0.546 P=0.092 | |POLY 1.5 | P=0.006 ** (e) P=0.531 P=0.082 | |POLY 6 | P=0.007 ** (e) P=0.565 P=0.106 | |LOGISTIC REGRESSION| P=0.005 ** (e) P=0.610 P=0.065 | |COCH-ARM / FISHERS | P=0.005 ** (e) P=0.510 P=0.064 | |ORDER RESTRICTED | P=0.013 * (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 40 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 4/55 (7%) 2/53 (4%) 4/53 (8%) | |POLY-3 RATE (b) | 0/31.35 4/39.52 2/39.60 4/38.50 | |POLY-3 PERCENT (g) | 0.0% 10.1% 5.1% 10.4% | |TERMINAL (d) | 0/15 (0%) 2/25 (8%) 2/26 (8%) 2/22 (9%) | |FIRST INCIDENCE | --- 253 727 (T) 448 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.196 P=0.132 P=0.365 P=0.106 | |POLY 3 | P=0.207 P=0.094 P=0.292 P=0.089 | |POLY 1.5 | P=0.187 P=0.082 P=0.273 P=0.081 | |POLY 6 | P=0.228 P=0.114 P=0.316 P=0.099 | |LOGISTIC REGRESSION| P=0.160 P=0.074 P=0.365 P=0.073 | |COCH-ARM / FISHERS | P=0.148 P=0.069 P=0.257 P=0.064 | |ORDER RESTRICTED | P=0.072 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Parathyroid Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/47 (0%) 1/50 (2%) 1/48 (2%) 2/46 (4%) | |POLY-3 RATE (b) | 0/27.62 1/35.62 1/37.40 2/34.68 | |POLY-3 PERCENT (g) | 0.0% 2.8% 2.7% 5.8% | |TERMINAL (d) | 0/13 (0%) 1/24 (4%) 0/24 (0%) 0/21 (0%) | |FIRST INCIDENCE | --- 727 (T) 376 559 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.183 P=0.622 P=0.521 P=0.283 | |POLY 3 | P=0.193 P=0.550 P=0.559 P=0.291 | |POLY 1.5 | P=0.178 P=0.535 P=0.541 P=0.271 | |POLY 6 | P=0.207 P=0.571 P=0.580 P=0.313 | |LOGISTIC REGRESSION| P=0.117 P=0.622 P=0.376 P=0.217 | |COCH-ARM / FISHERS | P=0.142 P=0.515 P=0.505 P=0.242 | |ORDER RESTRICTED | P=0.160 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 41 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Pituitary Gland | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 14/51 (27%) 15/54 (28%) 22/53 (42%) 12/53 (23%) | |POLY-3 RATE (b) | 14/33.32 15/40.05 22/44.01 12/38.05 | |POLY-3 PERCENT (g) | 42.0% 37.5% 50.0% 31.5% | |TERMINAL (d) | 7/15 (47%) 7/25 (28%) 13/26 (50%) 10/22 (46%) | |FIRST INCIDENCE | 546 434 328 487 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.238N P=0.194N P=0.572 P=0.108N | |POLY 3 | P=0.337N P=0.436N P=0.317 P=0.243N | |POLY 1.5 | P=0.331N P=0.507N P=0.223 P=0.262N | |POLY 6 | P=0.410N P=0.337N P=0.433 P=0.252N | |LOGISTIC REGRESSION| P=0.295N P=0.422N P=0.225 P=0.176N | |COCH-ARM / FISHERS | P=0.457N P=0.572 P=0.097 P=0.367N | |ORDER RESTRICTED | P=0.247N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Pituitary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 3/54 (6%) 1/53 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 0/30.88 3/38.75 1/39.60 1/37.76 | |POLY-3 PERCENT (g) | 0.0% 7.7% 2.5% 2.7% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE | --- 448 727 (T) 600 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.497N P=0.187 P=0.610 P=0.531 | |POLY 3 | P=0.469N P=0.163 P=0.549 P=0.540 | |POLY 1.5 | P=0.494N P=0.148 P=0.535 P=0.531 | |POLY 6 | P=0.446N P=0.189 P=0.566 P=0.549 | |LOGISTIC REGRESSION| P=0.536N P=0.134 P=0.610 P=0.508 | |COCH-ARM / FISHERS | P=0.550N P=0.132 P=0.510 P=0.510 | |ORDER RESTRICTED | P=0.276 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 42 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 18/51 (35%) 20/54 (37%) 23/53 (43%) 17/53 (32%) | |POLY-3 RATE (b) | 18/36.64 20/40.01 23/42.91 17/41.61 | |POLY-3 PERCENT (g) | 49.1% 50.0% 53.6% 40.9% | |TERMINAL (d) | 4/15 (27%) 13/25 (52%) 15/26 (58%) 8/22 (36%) | |FIRST INCIDENCE | 400 546 498 436 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.222N P=0.215N P=0.328N P=0.208N | |POLY 3 | P=0.254N P=0.562 P=0.429 P=0.301N | |POLY 1.5 | P=0.273N P=0.545 P=0.382 P=0.317N | |POLY 6 | P=0.279N P=0.593 P=0.465 P=0.318N | |LOGISTIC REGRESSION| P=0.270N P=0.501N P=0.475 P=0.326N | |COCH-ARM / FISHERS | P=0.438N P=0.507 P=0.260 P=0.444N | |ORDER RESTRICTED | P=0.286N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 39/52 (75%) 43/55 (78%) 46/52 (88%) 45/53 (85%) | |POLY-3 RATE (b) | 39/47.51 43/47.53 46/48.28 45/49.58 | |POLY-3 PERCENT (g) | 82.1% 90.5% 95.3% 90.8% | |TERMINAL (d) | 8/15 (53%) 23/25 (92%) 24/25 (96%) 21/22 (96%) | |FIRST INCIDENCE | 126 223 188 385 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.442N P=0.112N P=0.174N P=0.336N | |POLY 3 | P=0.096 P=0.170 P=0.033 * P=0.155 | |POLY 1.5 | P=0.093 P=0.251 P=0.039 * P=0.168 | |POLY 6 | P=0.078 P=0.114 P=0.032 * P=0.119 | |LOGISTIC REGRESSION| P=0.162 P=0.522 P=0.115 P=0.202 | |COCH-ARM / FISHERS | P=0.068 P=0.436 P=0.063 P=0.153 | |ORDER RESTRICTED | P=0.035 * (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 43 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 49/52 (94%) 50/55 (91%) 51/52 (98%) 51/53 (96%) | |POLY-3 RATE (b) | 49/49.42 50/52.81 51/51.32 51/52.28 | |POLY-3 PERCENT (g) | 99.2% 94.7% 99.4% 97.6% | |TERMINAL (d) | 15/15 (100%) 24/25 (96%) 25/25 (100%) 22/22 (100%) | |FIRST INCIDENCE | 126 202 188 124 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.208N P=0.030N* P=0.026N* P=0.114N | |POLY 3 | P=0.518 P=0.209N P=0.972 P=0.575N | |POLY 1.5 | P=0.449 P=0.266N P=0.743 P=0.634N | |POLY 6 | P=0.489 P=0.189N P=1.000 P=0.678N | |LOGISTIC REGRESSION| P=0.295 P=0.320N P=0.493 P=0.672 | |COCH-ARM / FISHERS | P=0.180 P=0.390N P=0.309 P=0.491 | |ORDER RESTRICTED | P=0.355N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 5/55 (9%) 3/52 (6%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.36 5/42.56 3/40.37 2/38.51 | |POLY-3 PERCENT (g) | 0.0% 11.8% 7.4% 5.2% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/25 (4%) 0/22 (0%) | |FIRST INCIDENCE | --- 202 328 500 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.560 P=0.049 * P=0.167 P=0.272 | |POLY 3 | P=0.527N P=0.065 P=0.170 P=0.285 | |POLY 1.5 | P=0.562N P=0.052 P=0.150 P=0.271 | |POLY 6 | P=0.500N P=0.088 P=0.195 P=0.300 | |LOGISTIC REGRESSION| P=0.291 P=0.022 * P=0.070 P=0.202 | |COCH-ARM / FISHERS | P=0.496 P=0.033 * P=0.121 P=0.252 | |ORDER RESTRICTED | P=0.146 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 44 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Spleen: Red Pulp | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/55 (0%) 4/52 (8%) 1/53 (2%) | |POLY-3 RATE (b) | 0/31.36 0/38.53 4/40.50 1/38.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 9.9% 2.6% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/25 (4%) 0/22 (0%) | |FIRST INCIDENCE | --- --- 328 500 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.174 (e) P=0.113 P=0.524 | |POLY 3 | P=0.180 (e) P=0.099 P=0.538 | |POLY 1.5 | P=0.174 (e) P=0.083 P=0.528 | |POLY 6 | P=0.178 (e) P=0.122 P=0.549 | |LOGISTIC REGRESSION| P=0.109 (e) P=0.042 * P=0.453 | |COCH-ARM / FISHERS | P=0.146 (e) P=0.059 P=0.505 | |ORDER RESTRICTED | P=0.119 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 3/55 (5%) 1/53 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 0/31.36 3/38.71 1/39.75 1/37.58 | |POLY-3 PERCENT (g) | 0.0% 7.8% 2.5% 2.7% | |TERMINAL (d) | 0/15 (0%) 2/25 (8%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- 681 688 658 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.499N P=0.226 P=0.595 P=0.568 | |POLY 3 | P=0.477N P=0.159 P=0.547 P=0.536 | |POLY 1.5 | P=0.503N P=0.145 P=0.531 P=0.527 | |POLY 6 | P=0.450N P=0.184 P=0.566 P=0.546 | |LOGISTIC REGRESSION| P=0.514N P=0.193 P=0.557 P=0.530 | |COCH-ARM / FISHERS | P=0.558N P=0.132 P=0.505 P=0.505 | |ORDER RESTRICTED | P=0.273 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 45 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/52 (6%) 4/55 (7%) 6/53 (11%) 2/53 (4%) | |POLY-3 RATE (b) | 3/32.29 4/38.74 6/41.70 2/38.13 | |POLY-3 PERCENT (g) | 9.3% 10.3% 14.4% 5.3% | |TERMINAL (d) | 1/15 (7%) 2/25 (8%) 2/26 (8%) 0/22 (0%) | |FIRST INCIDENCE | 391 681 328 559 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.348N P=0.567N P=0.446 P=0.377N | |POLY 3 | P=0.357N P=0.600 P=0.381 P=0.424N | |POLY 1.5 | P=0.376N P=0.567 P=0.331 P=0.444N | |POLY 6 | P=0.350N P=0.649 P=0.446 P=0.403N | |LOGISTIC REGRESSION| P=0.417N P=0.605 P=0.246 P=0.483N | |COCH-ARM / FISHERS | P=0.445N P=0.532 P=0.254 P=0.491N | |ORDER RESTRICTED | P=0.315N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 1/55 (2%) 2/53 (4%) 1/53 (2%) | |POLY-3 RATE (b) | 0/31.36 1/38.56 2/40.19 1/37.58 | |POLY-3 PERCENT (g) | 0.0% 2.6% 5.0% 2.7% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | --- 720 602 658 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.361 P=0.624 P=0.328 P=0.568 | |POLY 3 | P=0.375 P=0.541 P=0.296 P=0.536 | |POLY 1.5 | P=0.363 P=0.528 P=0.275 P=0.527 | |POLY 6 | P=0.385 P=0.561 P=0.324 P=0.546 | |LOGISTIC REGRESSION| P=0.345 P=0.596 P=0.263 P=0.530 | |COCH-ARM / FISHERS | P=0.319 P=0.514 P=0.252 P=0.505 | |ORDER RESTRICTED | P=0.276 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 46 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/52 (6%) 1/55 (2%) 0/53 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 3/32.17 1/38.56 0/39.60 1/37.58 | |POLY-3 PERCENT (g) | 9.3% 2.6% 0.0% 2.7% | |TERMINAL (d) | 1/15 (7%) 0/25 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 574 720 --- 658 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.135N P=0.180N P=0.066N P=0.217N | |POLY 3 | P=0.170N P=0.242N P=0.085N P=0.250N | |POLY 1.5 | P=0.169N P=0.260N P=0.095N P=0.262N | |POLY 6 | P=0.176N P=0.216N P=0.075N P=0.240N | |LOGISTIC REGRESSION| P=0.153N P=0.239N P=0.094N P=0.258N | |COCH-ARM / FISHERS | P=0.176N P=0.288N P=0.118N P=0.302N | |ORDER RESTRICTED | P=0.052N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 37/50 (74%) 34/52 (65%) 41/46 (89%) 45/48 (94%) | |POLY-3 RATE (b) | 37/45.02 34/44.40 41/43.90 45/45.61 | |POLY-3 PERCENT (g) | 82.2% 76.6% 93.4% 98.7% | |TERMINAL (d) | 9/15 (60%) 15/22 (68%) 19/21 (91%) 19/19 (100%) | |FIRST INCIDENCE | 126 202 300 385 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.230 P=0.052N P=0.203N P=0.543N | |POLY 3 | P<0.001 ** P=0.340N P=0.088 P=0.005 ** | |POLY 1.5 | P<0.001 ** P=0.297N P=0.063 P=0.005 ** | |POLY 6 | P<0.001 ** P=0.376N P=0.117 P=0.006 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.196N P=0.081 P=0.018 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.233N P=0.050 P=0.008 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 47 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Thyroid Gland | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 1/55 (2%) 4/52 (8%) 0/51 (0%) | |POLY-3 RATE (b) | 0/31.37 1/38.53 4/39.64 0/36.51 | |POLY-3 PERCENT (g) | 0.0% 2.6% 10.1% 0.0% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 3/26 (12%) 0/22 (0%) | |FIRST INCIDENCE | --- 727 (T) 709 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.543 P=0.602 P=0.154 (e) | |POLY 3 | P=0.535 P=0.541 P=0.095 (e) | |POLY 1.5 | P=0.517 P=0.527 P=0.081 (e) | |POLY 6 | P=0.542 P=0.561 P=0.114 (e) | |LOGISTIC REGRESSION| P=0.524 P=0.602 P=0.137 (e) | |COCH-ARM / FISHERS | P=0.455 P=0.514 P=0.059 (e) | |ORDER RESTRICTED | P=0.194 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/52 (23%) 21/55 (38%) 17/52 (33%) 19/51 (37%) | |POLY-3 RATE (b) | 12/33.93 21/40.89 17/42.41 19/40.46 | |POLY-3 PERCENT (g) | 35.4% 51.4% 40.1% 47.0% | |TERMINAL (d) | 5/15 (33%) 14/25 (56%) 10/26 (39%) 11/22 (50%) | |FIRST INCIDENCE | 541 356 428 436 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.478 P=0.427 P=0.463N P=0.384 | |POLY 3 | P=0.401 P=0.115 P=0.426 P=0.212 | |POLY 1.5 | P=0.328 P=0.088 P=0.334 P=0.165 | |POLY 6 | P=0.451 P=0.169 P=0.532 P=0.260 | |LOGISTIC REGRESSION| P=0.315 P=0.152 P=0.399 P=0.180 | |COCH-ARM / FISHERS | P=0.171 P=0.069 P=0.191 P=0.088 | |ORDER RESTRICTED | P=0.250 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 48 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/52 (17%) 13/55 (24%) 13/52 (25%) 17/51 (33%) | |POLY-3 RATE (b) | 9/37.19 13/42.20 13/42.54 17/40.34 | |POLY-3 PERCENT (g) | 24.2% 30.8% 30.6% 42.2% | |TERMINAL (d) | 2/15 (13%) 5/25 (20%) 6/26 (23%) 9/22 (41%) | |FIRST INCIDENCE | 201 448 498 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.159 P=0.517 P=0.549 P=0.210 | |POLY 3 | P=0.065 P=0.341 P=0.350 P=0.069 | |POLY 1.5 | P=0.057 P=0.292 P=0.294 P=0.059 | |POLY 6 | P=0.072 P=0.444 P=0.445 P=0.091 | |LOGISTIC REGRESSION| P=0.040 * P=0.246 P=0.135 P=0.030 * | |COCH-ARM / FISHERS | P=0.043 * P=0.285 P=0.236 P=0.050 | |ORDER RESTRICTED | P=0.067 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Tooth: Peridontal Tissue | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/12 (83%) 12/12 (100%) 10/10 (100%) 9/9 (100%) | |POLY-3 RATE (b) | 10/12.00 12/12.00 10/10.00 9/9.00 | |POLY-3 PERCENT (g) | 83.3% 100.0% 100.0% 100.0% | |TERMINAL (d) | 5/7 (71%) 9/9 (100%) 5/5 (100%) 4/4 (100%) | |FIRST INCIDENCE | 405 253 300 436 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.361 P=0.515N P=0.610 P=0.574 | |POLY 3 | P=0.133 P=0.229 P=0.272 P=0.297 | |POLY 1.5 | P=0.133 P=0.229 P=0.272 P=0.297 | |POLY 6 | P=0.133 P=0.229 P=0.272 P=0.297 | |LOGISTIC REGRESSION| (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.138 P=0.239 P=0.286 P=0.314 | |ORDER RESTRICTED | P=0.054 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 49 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Tooth: Peridontal Tissue | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/12 (17%) 0/12 (0%) 0/10 (0%) 0/9 (0%) | |POLY-3 RATE (b) | 2/9.81 0/10.52 0/7.71 0/6.56 | |POLY-3 PERCENT (g) | 20.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/7 (29%) 0/9 (0%) 0/5 (0%) 0/4 (0%) | |FIRST INCIDENCE | 727 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.173N P=0.178N P=0.308N P=0.362N | |POLY 3 | P=0.147N P=0.210N P=0.283N P=0.324N | |POLY 1.5 | P=0.138N P=0.221N P=0.284N P=0.310N | |POLY 6 | P=0.162N P=0.196N P=0.277N P=0.346N | |LOGISTIC REGRESSION| P=0.173N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.138N P=0.239N P=0.286N P=0.314N | |ORDER RESTRICTED | P=0.072N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Urinary Bladder | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/51 (8%) 6/54 (11%) 10/53 (19%) 6/52 (12%) | |POLY-3 RATE (b) | 4/32.86 6/41.99 10/43.51 6/38.88 | |POLY-3 PERCENT (g) | 12.2% 14.3% 23.0% 15.4% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 5/26 (19%) 1/22 (5%) | |FIRST INCIDENCE | 391 350 188 448 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.375 P=0.496 P=0.216 P=0.526 | |POLY 3 | P=0.331 P=0.530 P=0.183 P=0.478 | |POLY 1.5 | P=0.321 P=0.479 P=0.146 P=0.451 | |POLY 6 | P=0.330 P=0.592 P=0.227 P=0.507 | |LOGISTIC REGRESSION| P=0.182 P=0.356 P=0.052 P=0.374 | |COCH-ARM / FISHERS | P=0.257 P=0.408 P=0.086 P=0.383 | |ORDER RESTRICTED | P=0.343 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 50 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Urinary Bladder: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/51 (2%) 1/54 (2%) 1/53 (2%) 2/52 (4%) | |POLY-3 RATE (b) | 1/31.35 1/38.94 1/40.46 2/37.45 | |POLY-3 PERCENT (g) | 3.2% 2.6% 2.5% 5.3% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) | |FIRST INCIDENCE | 574 524 376 658 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.396 P=0.730N P=0.727N P=0.598 | |POLY 3 | P=0.376 P=0.711N P=0.701N P=0.562 | |POLY 1.5 | P=0.371 P=0.728N P=0.720N P=0.546 | |POLY 6 | P=0.376 P=0.687N P=0.680N P=0.577 | |LOGISTIC REGRESSION| P=0.300 P=0.761N P=0.709 P=0.531 | |COCH-ARM / FISHERS | P=0.340 P=0.738N P=0.743N P=0.507 | |ORDER RESTRICTED | P=0.448 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/52 (23%) 12/55 (22%) 11/53 (21%) 16/52 (31%) | |POLY-3 RATE (b) | 12/35.65 12/42.38 11/42.96 16/40.30 | |POLY-3 PERCENT (g) | 33.7% 28.3% 25.6% 39.7% | |TERMINAL (d) | 2/15 (13%) 4/25 (16%) 4/26 (15%) 9/22 (41%) | |FIRST INCIDENCE | 391 328 188 448 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.386 P=0.257N P=0.194N P=0.558 | |POLY 3 | P=0.264 P=0.395N P=0.296N P=0.377 | |POLY 1.5 | P=0.256 P=0.445N P=0.350N P=0.348 | |POLY 6 | P=0.258 P=0.341N P=0.244N P=0.391 | |LOGISTIC REGRESSION| P=0.220 P=0.507N P=0.452N P=0.351 | |COCH-ARM / FISHERS | P=0.194 P=0.530N P=0.479N P=0.254 | |ORDER RESTRICTED | P=0.254 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 51 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/55 (0%) 0/53 (0%) 2/52 (4%) | |POLY-3 RATE (b) | 0/31.36 0/38.53 0/39.60 2/36.94 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.4% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 2/22 (9%) | |FIRST INCIDENCE | --- --- --- 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.051 (e) (e) P=0.325 | |POLY 3 | P=0.048 * (e) (e) P=0.274 | |POLY 1.5 | P=0.047 * (e) (e) P=0.263 | |POLY 6 | P=0.048 * (e) (e) P=0.286 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.325 | |COCH-ARM / FISHERS | P=0.044 * (e) (e) P=0.248 | |ORDER RESTRICTED | P=0.045 * (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 26/52 (50%) 33/55 (60%) 25/53 (47%) 28/52 (54%) | |POLY-3 RATE (b) | 26/41.07 33/47.72 25/45.60 28/45.56 | |POLY-3 PERCENT (g) | 63.3% 69.2% 54.8% 61.5% | |TERMINAL (d) | 7/15 (47%) 16/25 (64%) 11/26 (42%) 12/22 (55%) | |FIRST INCIDENCE | 321 253 188 385 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.170N P=0.391N P=0.073N P=0.291N | |POLY 3 | P=0.263N P=0.356 P=0.275N P=0.518N | |POLY 1.5 | P=0.291N P=0.306 P=0.313N P=0.557N | |POLY 6 | P=0.263N P=0.379 P=0.246N P=0.523N | |LOGISTIC REGRESSION| P=0.394N P=0.240 P=0.362N P=0.494 | |COCH-ARM / FISHERS | P=0.458N P=0.199 P=0.462N P=0.422 | |ORDER RESTRICTED | P=0.330N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 52 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/55 (0%) 2/53 (4%) 0/52 (0%) | |POLY-3 RATE (b) | 0/31.36 0/38.53 2/39.98 0/36.94 | |POLY-3 PERCENT (g) | 0.0% 0.0% 5.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/26 (4%) 0/22 (0%) | |FIRST INCIDENCE | --- --- 621 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.494 (e) P=0.351 (e) | |POLY 3 | P=0.497 (e) P=0.294 (e) | |POLY 1.5 | P=0.492 (e) P=0.274 (e) | |POLY 6 | P=0.493 (e) P=0.321 (e) | |LOGISTIC REGRESSION| P=0.478 (e) P=0.285 (e) | |COCH-ARM / FISHERS | P=0.453 (e) P=0.252 (e) | |ORDER RESTRICTED | P=0.296 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 | | | NG/KG NG/KG | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 23/52 (44%) 33/55 (60%) 28/53 (53%) 24/52 (46%) | |POLY-3 RATE (b) | 23/35.31 33/43.07 28/43.94 24/42.67 | |POLY-3 PERCENT (g) | 65.1% 76.6% 63.7% 56.3% | |TERMINAL (d) | 12/15 (80%) 22/25 (88%) 16/26 (62%) 11/22 (50%) | |FIRST INCIDENCE | 496 350 188 385 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.090N P=0.438N P=0.161N P=0.194N | |POLY 3 | P=0.053N P=0.165 P=0.545N P=0.273N | |POLY 1.5 | P=0.109N P=0.107 P=0.497 P=0.391N | |POLY 6 | P=0.029N* P=0.288 P=0.371N P=0.181N | |LOGISTIC REGRESSION| P=0.144N P=0.187 P=0.556N P=0.389N | |COCH-ARM / FISHERS | P=0.380N P=0.075 P=0.246 P=0.500 | |ORDER RESTRICTED | P=0.107N (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).