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: 12:23:10 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. TREATED 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 INCLUDE 006 300 NG/KG INCLUDE 007 550 NG/KG INCLUDE 008 1000 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: 12:23:10 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 Atrophy Hyperplasia Hypertrophy Vacuolization Cytoplasmic Adrenal Medulla Hyperplasia Blood Vessel: Aorta Mineralization Bone Marrow Hyperplasia Clitoral Gland Inflammation Clitoral Gland: Duct Cyst Eye: Cornea Inflammation Eye: Retina Atrophy Harderian Gland Inflammation Heart Cardiomyopathy Heart: Epicardium Inflammation Intestine Small, Duodenum Erosion Kidney Casts Protein Mineralization Nephropathy Kidney: Transitional Epithelium Hyperplasia Liver Basophilic Focus Cholangiofibrosis Clear Cell Focus Degeneration Cystic Eosinophilic Focus Fatty Change Diffuse Fatty Change Focal Hepatocyte, Multinucleate Hyperplasia Inflammation Mixed Cell Focus Necrosis Pigmentation Toxic Hepatopathy Liver: Bile Duct Cyst Hyperplasia Liver: Hepatocyte Degeneration Hypertrophy Liver: Oval Cell Hyperplasia Liver: Portal Fibrosis Lung Infiltration Cellular Histiocyte Inflammation Chronic Inflammation Granulomatous Metaplasia Lung: Alveolar Epithelium Hyperplasia Metaplasia Bronchiolar Lymph Node, Mandibular Ectasia Hyperplasia 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: 12:23:10 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-75411 ROUTE: GAVAGE NTP C#: 96007D PATHOLOGIST: MISSING CAS: 57465-28-8 Lymph Node, Mesenteric Hyperplasia Hyperplasia Lymphoid Lymph Node: Mediastinal Ectasia Hemorrhage Pigmentation Mammary Gland Cyst Hyperplasia Mesentery Inflammation Chronic Mesentery: Artery Inflammation Chronic Nose: Turbinate Inflammation Oral Mucosa: Gingival Hyperplasia Ovary Atrophy Pancreas Inflammation Chronic Pancreas: Acinus Atrophy Vacuolization Cytoplasmic Pancreas: Artery Inflammation Chronic Pancreas: Duct Dilatation Pituitary Gland: Pars Distalis Hyperplasia Spleen Hematopoietic Cell Proliferation Hyperplasia Lymphoid Pigmentation Spleen: Lymphoid Follicle Atrophy Spleen: Red Pulp Atrophy Stomach, Forestomach Hyperplasia Thymus Atrophy Thyroid Gland: C-Cell Hyperplasia Thyroid Gland: Follicular Cell Hypertrophy Tooth: Peridontal Tissue Inflammation Inflammation Chronic Ureter Metaplasia Uterus Inflammation Metaplasia Uterus: Endometrium Hyperplasia Cystic =============================================================== 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/52 (21%) 13/55 (24%) 25/53 (47%) 19/53 (36%) 20/53 (38%) 8/52 (15%) 1/53 (2%) | |POLY-3 RATE (b) | 11/34.50 13/39.17 25/43.24 19/38.60 20/39.31 8/42.81 1/32.22 | |POLY-3 PERCENT (g) | 31.9% 33.2% 57.8% 49.2% 50.9% 18.7% 3.1% | |TERMINAL (d) | 4/15 (27%) 12/25 (48%) 16/26 (62%) 14/22 (64%) 12/16 (75%) 6/23 (26%) 0/7 (0%) | |FIRST INCIDENCE | 541 516 498 658 301 440 642 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001N** P=0.327N P=0.148 P=0.299 P=0.106 P=0.078N P=0.010N* | |POLY 3 | P<0.001N** P=0.553 P=0.016 * P=0.092 P=0.069 P=0.140N P=0.002N** | |POLY 1.5 | P<0.001N** P=0.519 P=0.009 ** P=0.096 P=0.063 P=0.183N P=0.002N** | |POLY 6 | P<0.001N** P=0.594 P=0.028 * P=0.078 P=0.061 P=0.109N P=0.004N** | |LOGISTIC REGRESSION| P<0.001N** P=0.541N P=0.019 * P=0.167 P=0.095 P=0.179N P=0.002N** | |COCH-ARM / FISHERS | P<0.001N** P=0.470 P=0.004 ** P=0.073 P=0.049 * P=0.306N P=0.002N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 3/55 (5%) 5/53 (9%) 3/53 (6%) 5/53 (9%) 19/52 (37%) 30/53 (57%) | |POLY-3 RATE (b) | 1/31.36 3/38.64 5/41.14 3/38.30 5/37.66 19/43.48 30/39.85 | |POLY-3 PERCENT (g) | 3.2% 7.8% 12.2% 7.8% 13.3% 43.7% 75.3% | |TERMINAL (d) | 1/15 (7%) 2/25 (8%) 3/26 (12%) 0/22 (0%) 2/16 (13%) 9/23 (39%) 6/7 (86%) | |FIRST INCIDENCE | 727 (T) 700 300 592 607 554 243 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.502 P=0.218 P=0.410 P=0.150 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.382 P=0.176 P=0.379 P=0.146 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.356 P=0.148 P=0.357 P=0.129 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.424 P=0.214 P=0.405 P=0.167 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.486 P=0.115 P=0.358 P=0.143 P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.330 P=0.107 P=0.316 P=0.107 P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/52 (21%) 14/55 (25%) 10/53 (19%) 14/53 (26%) 14/53 (26%) 16/52 (31%) 10/53 (19%) | |POLY-3 RATE (b) | 11/34.41 14/40.34 10/40.23 14/39.18 14/40.61 16/43.78 10/35.87 | |POLY-3 PERCENT (g) | 32.0% 34.7% 24.9% 35.7% 34.5% 36.5% 27.9% | |TERMINAL (d) | 4/15 (27%) 9/25 (36%) 7/26 (27%) 9/22 (41%) 0/16 (0%) 8/23 (35%) 0/7 (0%) | |FIRST INCIDENCE | 496 516 651 496 531 535 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.127 P=0.423N P=0.134N P=0.539N P=0.548 P=0.528N P=0.515 | |POLY 3 | P=0.484N P=0.498 P=0.334N P=0.462 P=0.507 P=0.427 P=0.454N | |POLY 1.5 | P=0.464N P=0.446 P=0.379N P=0.437 P=0.440 P=0.336 P=0.448N | |POLY 6 | P=0.500 P=0.576 P=0.290N P=0.474 P=0.581 P=0.525 P=0.504N | |LOGISTIC REGRESSION| P=0.520N P=0.526 P=0.277N P=0.506 P=0.428 P=0.391 P=0.471N | |COCH-ARM / FISHERS | P=0.473N P=0.384 P=0.480N P=0.344 P=0.344 P=0.186 P=0.480N | |ORDER RESTRICTED | P=0.590N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 23/52 (44%) 21/55 (38%) 27/53 (51%) 25/53 (47%) 25/53 (47%) 31/52 (60%) 24/53 (45%) | |POLY-3 RATE (b) | 23/38.88 21/40.99 27/43.02 25/42.19 25/41.73 31/44.16 24/39.04 | |POLY-3 PERCENT (g) | 59.2% 51.2% 62.8% 59.3% 59.9% 70.2% 61.5% | |TERMINAL (d) | 7/15 (47%) 15/25 (60%) 16/26 (62%) 12/22 (55%) 10/16 (63%) 18/23 (78%) 4/7 (57%) | |FIRST INCIDENCE | 309 434 531 530 331 573 394 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** P=0.046N* P=0.181N P=0.289N P=0.453N P=0.341N P=0.230 | |POLY 3 | P=0.189 P=0.305N P=0.455 P=0.590 P=0.566 P=0.191 P=0.509 | |POLY 1.5 | P=0.224 P=0.312N P=0.410 P=0.571 P=0.534 P=0.155 P=0.538 | |POLY 6 | P=0.119 P=0.300N P=0.510 P=0.594 P=0.572 P=0.219 P=0.419 | |LOGISTIC REGRESSION| P=0.204 P=0.200N P=0.576 P=0.508N P=0.565N P=0.363 P=0.567 | |COCH-ARM / FISHERS | P=0.257 P=0.330N P=0.311 P=0.458 P=0.458 P=0.085 P=0.535 | |ORDER RESTRICTED | P=0.279 (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 34/52 (65%) 41/55 (75%) 40/53 (75%) 41/53 (77%) 40/53 (75%) 41/52 (79%) 41/53 (77%) | |POLY-3 RATE (b) | 34/39.07 41/45.61 40/45.30 41/44.98 40/45.32 41/46.88 41/44.54 | |POLY-3 PERCENT (g) | 87.0% 89.9% 88.3% 91.2% 88.3% 87.5% 92.0% | |TERMINAL (d) | 15/15 (100%) 22/25 (88%) 24/26 (92%) 22/22 (100%) 14/16 (88%) 22/23 (96%) 7/7 (100%) | |FIRST INCIDENCE | 391 356 498 405 454 185 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.129N P=0.060N P=0.313N P=0.558 P=0.095N P=0.013 * | |POLY 3 | P=0.353 P=0.464 P=0.575 P=0.360 P=0.575 P=0.625 P=0.299 | |POLY 1.5 | P=0.272 P=0.290 P=0.381 P=0.278 P=0.341 P=0.383 P=0.188 | |POLY 6 | P=0.399 P=0.606N P=0.556N P=0.462 P=0.470N P=0.465N P=0.534 | |LOGISTIC REGRESSION| P=0.197 P=0.369 P=0.539N P=0.477 P=0.446 P=0.538N P=0.176 | |COCH-ARM / FISHERS | P=0.182 P=0.205 P=0.179 P=0.127 P=0.179 P=0.095 P=0.127 | |ORDER RESTRICTED | P=0.366 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 1/55 (2%) 0/53 (0%) 1/53 (2%) 1/53 (2%) 1/52 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 1/31.80 1/38.53 0/39.60 1/37.75 1/36.92 1/41.58 2/32.55 | |POLY-3 PERCENT (g) | 3.1% 2.6% 0.0% 2.7% 2.7% 2.4% 6.2% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 600 727 (T) --- 604 642 714 574 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.142 P=0.679N P=0.448N P=0.721N P=0.706N P=0.648N P=0.503 | |POLY 3 | P=0.195 P=0.717N P=0.456N P=0.722N P=0.727N P=0.698N P=0.508 | |POLY 1.5 | P=0.205 P=0.731N P=0.471N P=0.732N P=0.738N P=0.720N P=0.513 | |POLY 6 | P=0.187 P=0.695N P=0.440N P=0.713N P=0.717N P=0.672N P=0.484 | |LOGISTIC REGRESSION| P=0.206 P=0.724N P=0.499N P=0.761N P=0.750N P=0.731N P=0.509 | |COCH-ARM / FISHERS | P=0.216 P=0.738N P=0.495N P=0.748N P=0.748N P=0.752N P=0.507 | |ORDER RESTRICTED | P=0.296 (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/52 (10%) 3/55 (5%) 5/53 (9%) 2/53 (4%) 9/53 (17%) 4/52 (8%) 17/53 (32%) | |POLY-3 RATE (b) | 5/32.65 3/38.73 5/40.96 2/37.58 9/39.52 4/42.52 17/36.67 | |POLY-3 PERCENT (g) | 15.3% 7.8% 12.2% 5.3% 22.8% 9.4% 46.4% | |TERMINAL (d) | 3/15 (20%) 1/25 (4%) 2/26 (8%) 1/22 (5%) 2/16 (13%) 1/23 (4%) 3/7 (43%) | |FIRST INCIDENCE | 496 681 428 658 163 554 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.169N P=0.369N P=0.118N P=0.295 P=0.273N P<0.001 ** | |POLY 3 | P<0.001 ** P=0.263N P=0.483N P=0.159N P=0.308 P=0.338N P=0.004 ** | |POLY 1.5 | P<0.001 ** P=0.291N P=0.532N P=0.171N P=0.268 P=0.393N P=0.004 ** | |POLY 6 | P<0.001 ** P=0.223N P=0.422N P=0.148N P=0.358 P=0.281N P=0.003 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.256N P=0.560N P=0.161N P=0.224 P=0.422N P=0.004 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.327N P=0.617N P=0.211N P=0.206 P=0.500N P=0.004 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/55 (0%) 2/53 (4%) 1/53 (2%) 2/53 (4%) 2/52 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.36 0/38.53 2/39.67 1/37.32 2/36.61 2/41.53 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 0.0% 5.0% 2.7% 5.5% 4.8% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/26 (4%) 1/22 (5%) 2/16 (13%) 2/23 (9%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 709 727 (T) 727 (T) 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.391 (e) P=0.368 P=0.576 P=0.250 P=0.336 (e) | |POLY 3 | P=0.561 (e) P=0.292 P=0.535 P=0.272 P=0.304 (e) | |POLY 1.5 | P=0.577N (e) P=0.273 P=0.526 P=0.260 P=0.280 (e) | |POLY 6 | P=0.493 (e) P=0.318 P=0.543 P=0.283 P=0.333 (e) | |LOGISTIC REGRESSION| P=0.460 (e) P=0.341 P=0.576 P=0.250 P=0.336 (e) | |COCH-ARM / FISHERS | P=0.570N (e) P=0.252 P=0.505 P=0.252 P=0.248 (e) | |ORDER RESTRICTED | P=0.371 (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/52 (15%) 18/55 (33%) 11/53 (21%) 11/53 (21%) 12/53 (23%) 6/52 (12%) 1/53 (2%) | |POLY-3 RATE (b) | 8/33.72 18/40.38 11/41.48 11/39.17 12/37.67 6/42.16 1/32.28 | |POLY-3 PERCENT (g) | 23.7% 44.6% 26.5% 28.1% 31.9% 14.2% 3.1% | |TERMINAL (d) | 3/15 (20%) 12/25 (48%) 7/26 (27%) 7/22 (32%) 5/16 (31%) 3/23 (13%) 0/7 (0%) | |FIRST INCIDENCE | 496 580 376 496 618 573 621 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004N** P=0.208 P=0.511N P=0.566 P=0.376 P=0.143N P=0.040N* | |POLY 3 | P<0.001N** P=0.046 * P=0.496 P=0.438 P=0.305 P=0.224N P=0.015N* | |POLY 1.5 | P<0.001N** P=0.035 * P=0.434 P=0.409 P=0.283 P=0.273N P=0.014N* | |POLY 6 | P<0.001N** P=0.073 P=0.566 P=0.461 P=0.320 P=0.180N P=0.023N* | |LOGISTIC REGRESSION| P<0.001N** P=0.066 P=0.445 P=0.438 P=0.362 P=0.248N P=0.016N* | |COCH-ARM / FISHERS | P<0.001N** P=0.030 * P=0.323 P=0.323 P=0.243 P=0.387N P=0.014N* | |ORDER RESTRICTED | P=0.002N** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Blood Vessel: Aorta | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 1/55 (2%) 1/53 (2%) 0/53 (0%) 0/53 (0%) 2/53 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 3/32.76 1/39.50 1/40.46 0/37.32 0/36.61 2/42.83 0/31.91 | |POLY-3 PERCENT (g) | 9.2% 2.5% 2.5% 0.0% 0.0% 4.7% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 583 223 376 --- --- 573 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.203N P=0.255N P=0.239N P=0.097N P=0.088N P=0.329N P=0.100N | |POLY 3 | P=0.259N P=0.240N P=0.233N P=0.096N P=0.098N P=0.380N P=0.121N | |POLY 1.5 | P=0.240N P=0.259N P=0.255N P=0.100N P=0.104N P=0.418N P=0.116N | |POLY 6 | P=0.313N P=0.218N P=0.213N P=0.093N P=0.095N P=0.345N P=0.142N | |LOGISTIC REGRESSION| P=0.224N P=0.326N P=0.360N P=0.118N P=0.118N P=0.512N P=0.119N | |COCH-ARM / FISHERS | P=0.214N P=0.295N P=0.309N P=0.121N P=0.121N P=0.500N P=0.121N | |ORDER RESTRICTED | P=0.023N* (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Bone | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/55 (0%) 1/53 (2%) 0/53 (0%) 2/53 (4%) 0/53 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.38 0/38.53 1/39.88 0/37.32 2/38.22 0/42.13 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.5% 0.0% 5.2% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 651 --- 40 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.521N (e) P=0.595 (e) P=0.258 (e) (e) | |POLY 3 | P=0.461N (e) P=0.547 (e) P=0.283 (e) (e) | |POLY 1.5 | P=0.474N (e) P=0.531 (e) P=0.267 (e) (e) | |POLY 6 | P=0.485N (e) P=0.567 (e) P=0.299 (e) (e) | |LOGISTIC REGRESSION| P=0.513N (e) P=0.529 (e) P=0.182 (e) (e) | |COCH-ARM / FISHERS | P=0.504N (e) P=0.500 (e) P=0.248 (e) (e) | |ORDER RESTRICTED | P=0.507 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 47/53 (89%) 37/55 (67%) 35/53 (66%) 44/53 (83%) 45/53 (85%) 46/53 (87%) 46/53 (87%) | |POLY-3 RATE (b) | 47/52.12 37/50.34 35/50.58 44/52.04 45/51.59 46/52.30 46/49.04 | |POLY-3 PERCENT (g) | 90.2% 73.5% 69.2% 84.6% 87.2% 88.0% 93.8% | |TERMINAL (d) | 10/15 (67%) 14/25 (56%) 12/26 (46%) 16/22 (73%) 12/16 (75%) 18/23 (78%) 7/7 (100%) | |FIRST INCIDENCE | 126 223 188 124 40 185 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** P=0.004N** P=0.002N** P=0.072N P=0.181N P=0.019N* P=0.265 | |POLY 3 | P=0.006 ** P=0.022N* P=0.006N** P=0.282N P=0.432N P=0.479N P=0.370 | |POLY 1.5 | P=0.012 * P=0.016N* P=0.005N** P=0.272N P=0.399N P=0.476N P=0.545 | |POLY 6 | P=0.002 ** P=0.031N* P=0.008N** P=0.310N P=0.493N P=0.494N P=0.167 | |LOGISTIC REGRESSION| P=0.025 * P=0.010N* P=0.020N* P=0.436N P=0.504N P=0.514 P=0.508N | |COCH-ARM / FISHERS | P=0.025 * P=0.007N** P=0.005N** P=0.289N P=0.388N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.014 * (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Brain | | Hydrocephalus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 0/55 (0%) 2/53 (4%) 0/53 (0%) 0/53 (0%) 1/53 (2%) 0/53 (0%) | |POLY-3 RATE (b) | 1/32.36 0/38.53 2/39.86 0/37.32 0/36.61 1/42.15 0/31.91 | |POLY-3 PERCENT (g) | 3.1% 0.0% 5.0% 0.0% 0.0% 2.4% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 201 --- 678 --- --- 722 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.431N P=0.489N P=0.623 P=0.496N P=0.500N P=0.703N P=0.500N | |POLY 3 | P=0.349N P=0.465N P=0.572 P=0.472N P=0.475N P=0.699N P=0.503N | |POLY 1.5 | P=0.348N P=0.478N P=0.546 P=0.479N P=0.484N P=0.721N P=0.498N | |POLY 6 | P=0.385N P=0.447N P=0.605 P=0.464N P=0.467N P=0.673N P=0.520N | |LOGISTIC REGRESSION| P=0.354N P=0.524N P=0.434 P=0.710N P=0.511N P=0.650 P=0.515N | |COCH-ARM / FISHERS | P=0.352N P=0.491N P=0.500 P=0.500N P=0.500N P=0.752N P=0.500N | |ORDER RESTRICTED | P=0.323N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 28/50 (56%) 36/55 (65%) 39/52 (75%) 28/50 (56%) 30/53 (57%) 27/52 (52%) 22/51 (43%) | |POLY-3 RATE (b) | 28/40.18 36/47.35 39/48.96 28/42.13 30/44.65 27/47.18 22/42.43 | |POLY-3 PERCENT (g) | 69.7% 76.0% 79.7% 66.5% 67.2% 57.2% 51.9% | |TERMINAL (d) | 9/14 (64%) 19/25 (76%) 19/26 (73%) 13/22 (59%) 12/16 (75%) 11/23 (48%) 1/7 (14%) | |FIRST INCIDENCE | 222 253 188 436 301 320 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.365N P=0.325N P=0.406N P=0.134N P=0.385N P=0.043N* P=0.393N | |POLY 3 | P<0.001N** P=0.326 P=0.188 P=0.467N P=0.494N P=0.155N P=0.062N | |POLY 1.5 | P<0.001N** P=0.274 P=0.121 P=0.476N P=0.527N P=0.214N P=0.064N | |POLY 6 | P<0.001N** P=0.413 P=0.286 P=0.464N P=0.476N P=0.110N P=0.080N | |LOGISTIC REGRESSION| P=0.003N** P=0.287 P=0.055 P=0.424N P=0.513N P=0.321N P=0.150N | |COCH-ARM / FISHERS | P=0.004N** P=0.214 P=0.035 * P=0.580N P=0.554 P=0.415N P=0.137N | |ORDER RESTRICTED | P=0.012N* (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Clitoral Gland: Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 29/50 (58%) 32/55 (58%) 34/52 (65%) 37/50 (74%) 39/53 (74%) 42/52 (81%) 45/51 (88%) | |POLY-3 RATE (b) | 29/40.97 32/47.78 34/46.12 37/45.50 39/47.23 42/48.69 45/47.03 | |POLY-3 PERCENT (g) | 70.8% 67.0% 73.7% 81.3% 82.6% 86.3% 95.7% | |TERMINAL (d) | 8/14 (57%) 14/25 (56%) 17/26 (65%) 15/22 (68%) 11/16 (69%) 18/23 (78%) 6/7 (86%) | |FIRST INCIDENCE | 126 202 188 436 247 320 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.157N P=0.153N P=0.498N P=0.349 P=0.438N P=0.004 ** | |POLY 3 | P<0.001 ** P=0.435N P=0.472 P=0.170 P=0.126 P=0.049 * P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.497N P=0.402 P=0.117 P=0.090 P=0.025 * P<0.001 ** | |POLY 6 | P<0.001 ** P=0.377N P=0.557 P=0.260 P=0.177 P=0.094 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.562N P=0.383 P=0.113 P=0.100 P=0.033 * P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.571 P=0.287 P=0.069 P=0.072 P=0.011 * P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Esophagus: Muscularis | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 1/55 (2%) 0/53 (0%) 1/53 (2%) 1/53 (2%) 2/52 (4%) 0/52 (0%) | |POLY-3 RATE (b) | 2/30.96 1/39.04 0/39.60 1/37.32 1/36.86 2/41.73 0/31.53 | |POLY-3 PERCENT (g) | 6.5% 2.6% 0.0% 2.7% 2.7% 4.8% 0.0% | |TERMINAL (d) | 1/14 (7%) 0/25 (0%) 0/26 (0%) 1/22 (5%) 0/16 (0%) 2/23 (9%) 0/7 (0%) | |FIRST INCIDENCE | 547 574 --- 727 (T) 659 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.478N P=0.400N P=0.157N P=0.378N P=0.439N P=0.526N P=0.293N | |POLY 3 | P=0.421N P=0.420N P=0.186N P=0.435N P=0.439N P=0.582N P=0.231N | |POLY 1.5 | P=0.394N P=0.445N P=0.201N P=0.450N P=0.458N P=0.620N P=0.229N | |POLY 6 | P=0.494N P=0.384N P=0.170N P=0.421N P=0.421N P=0.540N P=0.247N | |LOGISTIC REGRESSION| P=0.368N P=0.463N P=0.205N P=0.430N P=0.455N P=0.574N P=0.231N | |COCH-ARM / FISHERS | P=0.363N P=0.479N P=0.243N P=0.493N P=0.493N P=0.691N P=0.248N | |ORDER RESTRICTED | P=0.129N (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Eye: Cornea | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/55 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 1/52 (2%) 2/52 (4%) | |POLY-3 RATE (b) | 0/30.21 0/38.53 0/39.60 0/37.32 0/36.61 1/41.54 2/31.74 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 2.4% 6.3% | |TERMINAL (d) | 0/14 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- --- 720 663 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P=0.610 P=0.208 | |POLY 3 | P=0.005 ** (e) (e) (e) (e) P=0.562 P=0.246 | |POLY 1.5 | P=0.006 ** (e) (e) (e) (e) P=0.543 P=0.249 | |POLY 6 | P=0.005 ** (e) (e) (e) (e) P=0.584 P=0.233 | |LOGISTIC REGRESSION| P=0.004 ** (e) (e) (e) (e) P=0.619 P=0.231 | |COCH-ARM / FISHERS | P=0.007 ** (e) (e) (e) (e) P=0.505 P=0.252 | |ORDER RESTRICTED | P=0.023 * (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Eye: Retina | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/55 (0%) 3/53 (6%) 1/53 (2%) 0/53 (0%) 1/52 (2%) 4/52 (8%) | |POLY-3 RATE (b) | 0/30.21 0/38.53 3/39.60 1/37.32 0/36.61 1/41.53 4/32.41 | |POLY-3 PERCENT (g) | 0.0% 0.0% 7.6% 2.7% 0.0% 2.4% 12.3% | |TERMINAL (d) | 0/14 (0%) 0/25 (0%) 3/26 (12%) 1/22 (5%) 0/16 (0%) 0/23 (0%) 1/7 (14%) | |FIRST INCIDENCE | --- --- 727 (T) 727 (T) --- 722 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) P=0.247 P=0.590 (e) P=0.602 P=0.031 * | |POLY 3 | P=0.022 * (e) P=0.173 P=0.542 (e) P=0.562 P=0.066 | |POLY 1.5 | P=0.020 * (e) P=0.155 P=0.533 (e) P=0.543 P=0.067 | |POLY 6 | P=0.024 * (e) P=0.198 P=0.551 (e) P=0.584 P=0.058 | |LOGISTIC REGRESSION| P=0.010 * (e) P=0.247 P=0.590 (e) P=0.622 P=0.066 | |COCH-ARM / FISHERS | P=0.018 * (e) P=0.129 P=0.510 (e) P=0.505 P=0.061 | |ORDER RESTRICTED | P=0.009 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Harderian Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 3/53 (6%) 6/53 (11%) 6/53 (11%) 3/53 (6%) 3/52 (6%) 6/52 (12%) | |POLY-3 RATE (b) | 2/32.88 3/38.60 6/39.67 6/37.35 3/37.08 3/42.38 6/33.83 | |POLY-3 PERCENT (g) | 6.1% 7.8% 15.1% 16.1% 8.1% 7.1% 17.7% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 5/26 (19%) 5/22 (23%) 0/16 (0%) 1/23 (4%) 1/7 (14%) | |FIRST INCIDENCE | 321 652 709 720 607 574 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.047 * P=0.643 P=0.315 P=0.260 P=0.581 P=0.632 P=0.110 | |POLY 3 | P=0.265 P=0.573 P=0.199 P=0.173 P=0.555 P=0.613 P=0.135 | |POLY 1.5 | P=0.264 P=0.543 P=0.175 P=0.165 P=0.536 P=0.573 P=0.139 | |POLY 6 | P=0.255 P=0.614 P=0.231 P=0.178 P=0.573 P=0.657 P=0.116 | |LOGISTIC REGRESSION| P=0.221 P=0.500 P=0.180 P=0.178 P=0.495 P=0.398 P=0.118 | |COCH-ARM / FISHERS | P=0.239 P=0.500 P=0.135 P=0.135 P=0.500 P=0.491 P=0.129 | |ORDER RESTRICTED | P=0.130 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/52 (17%) 16/54 (30%) 17/53 (32%) 16/53 (30%) 24/53 (45%) 28/51 (55%) 32/51 (63%) | |POLY-3 RATE (b) | 9/35.59 16/38.84 17/40.82 16/40.33 24/41.08 28/45.07 32/39.46 | |POLY-3 PERCENT (g) | 25.3% 41.2% 41.7% 39.7% 58.4% 62.1% 81.1% | |TERMINAL (d) | 2/15 (13%) 10/24 (42%) 14/26 (54%) 9/22 (41%) 12/16 (75%) 12/23 (52%) 7/7 (100%) | |FIRST INCIDENCE | 201 574 376 448 331 554 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.391 P=0.373 P=0.286 P=0.012 * P=0.034 * P<0.001 ** | |POLY 3 | P<0.001 ** P=0.107 P=0.096 P=0.132 P=0.002 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.096 P=0.082 P=0.120 P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.139 P=0.115 P=0.144 P=0.002 ** P=0.002 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.139 P=0.105 P=0.115 P=0.003 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.103 P=0.063 P=0.093 P=0.002 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Heart: Epicardium | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 0/54 (0%) 0/53 (0%) 1/53 (2%) 0/53 (0%) 0/51 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 2/32.82 0/37.53 0/39.60 1/38.32 0/36.61 0/41.13 0/30.95 | |POLY-3 PERCENT (g) | 6.1% 0.0% 0.0% 2.6% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/24 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 126 --- --- 124 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.178N P=0.218N P=0.215N P=0.482N P=0.217N P=0.204N P=0.228N | |POLY 3 | P=0.172N P=0.207N P=0.197N P=0.446N P=0.212N P=0.191N P=0.249N | |POLY 1.5 | P=0.177N P=0.218N P=0.210N P=0.458N P=0.221N P=0.208N P=0.244N | |POLY 6 | P=0.187N P=0.191N P=0.182N P=0.436N P=0.206N P=0.173N P=0.269N | |LOGISTIC REGRESSION| P=0.188N P=0.245N P=0.351N P=0.737 P=0.256N P=0.431N P=0.247N | |COCH-ARM / FISHERS | P=0.185N P=0.238N P=0.243N P=0.493N P=0.243N P=0.252N P=0.252N | |ORDER RESTRICTED | P=0.024N* (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG 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%) 0/53 (0%) 0/51 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 0/31.36 1/38.88 2/39.67 1/37.75 0/36.61 0/41.43 1/32.61 | |POLY-3 PERCENT (g) | 0.0% 2.6% 5.0% 2.7% 0.0% 0.0% 3.1% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/26 (4%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 630 709 604 --- --- 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.628 P=0.573 P=0.368 P=0.539 (e) (e) P=0.523 | |POLY 3 | P=0.470N P=0.543 P=0.292 P=0.537 (e) (e) P=0.508 | |POLY 1.5 | P=0.502N P=0.528 P=0.273 P=0.527 (e) (e) P=0.509 | |POLY 6 | P=0.446N P=0.564 P=0.318 P=0.547 (e) (e) P=0.495 | |LOGISTIC REGRESSION| P=0.556N P=0.522 P=0.341 P=0.506 (e) (e) P=0.496 | |COCH-ARM / FISHERS | P=0.554N P=0.514 P=0.252 P=0.505 (e) (e) P=0.505 | |ORDER RESTRICTED | P=0.382 (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG 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%) 1/53 (2%) 0/52 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 2/30.87 2/38.53 3/39.60 0/36.94 1/37.22 0/41.53 1/31.91 | |POLY-3 PERCENT (g) | 6.5% 5.2% 7.6% 0.0% 2.7% 0.0% 3.1% | |TERMINAL (d) | 2/15 (13%) 2/25 (8%) 3/26 (12%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 1/7 (14%) | |FIRST INCIDENCE | 727 (T) 727 (T) 727 (T) --- 531 --- 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.341N P=0.500N P=0.626N P=0.157N P=0.465N P=0.149N P=0.723 | |POLY 3 | P=0.152N P=0.612N P=0.612 P=0.198N P=0.435N P=0.178N P=0.488N | |POLY 1.5 | P=0.165N P=0.638N P=0.577 P=0.209N P=0.455N P=0.196N P=0.482N | |POLY 6 | P=0.144N P=0.574N P=0.652 P=0.189N P=0.416N P=0.160N P=0.518N | |LOGISTIC REGRESSION| P=0.219N P=0.500N P=0.626N (e) P=0.448N (e) P=0.723 | |COCH-ARM / FISHERS | P=0.186N P=0.670N P=0.509 P=0.248N P=0.493N P=0.248N P=0.493N | |ORDER RESTRICTED | P=0.281N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Intestine Small, Duodenum | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 0/55 (0%) 0/52 (0%) 0/53 (0%) 0/53 (0%) 0/51 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 1/31.84 0/38.53 0/38.67 0/37.32 0/36.61 0/41.43 2/32.17 | |POLY-3 PERCENT (g) | 3.1% 0.0% 0.0% 0.0% 0.0% 0.0% 6.2% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 583 --- --- --- --- --- 694 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.040 * P=0.471N P=0.455N P=0.471N P=0.461N P=0.436N P=0.455 | |POLY 3 | P=0.065 P=0.462N P=0.461N P=0.468N P=0.472N P=0.448N P=0.504 | |POLY 1.5 | P=0.065 P=0.474N P=0.475N P=0.476N P=0.481N P=0.467N P=0.511 | |POLY 6 | P=0.079 P=0.445N P=0.445N P=0.462N P=0.465N P=0.429N P=0.475 | |LOGISTIC REGRESSION| P=0.061 P=0.491N P=0.510N P=0.505N P=0.499N P=0.534N P=0.499 | |COCH-ARM / FISHERS | P=0.068 P=0.486N P=0.500N P=0.495N P=0.495N P=0.505N P=0.507 | |ORDER RESTRICTED | P=0.033 * (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Islets, Pancreatic | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 2/54 (4%) 1/53 (2%) 1/53 (2%) 0/53 (0%) 1/52 (2%) 0/51 (0%) | |POLY-3 RATE (b) | 1/31.36 2/39.02 1/40.16 1/37.75 0/36.61 1/41.53 0/30.67 | |POLY-3 PERCENT (g) | 3.2% 5.1% 2.5% 2.7% 0.0% 2.4% 0.0% | |TERMINAL (d) | 1/15 (7%) 1/25 (4%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | 727 (T) 223 555 604 --- 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.227N P=0.628 P=0.674N P=0.695N P=0.487N P=0.664N P=0.652N | |POLY 3 | P=0.183N P=0.576 P=0.703N P=0.719N P=0.469N P=0.694N P=0.504N | |POLY 1.5 | P=0.184N P=0.549 P=0.724N P=0.730N P=0.479N P=0.719N P=0.501N | |POLY 6 | P=0.201N P=0.613 P=0.676N P=0.706N P=0.460N P=0.666N P=0.519N | |LOGISTIC REGRESSION| P=0.188N P=0.501 P=0.740N P=0.727N (e) P=0.664N (e) | |COCH-ARM / FISHERS | P=0.187N P=0.514 P=0.748N P=0.748N P=0.495N P=0.752N P=0.505N | |ORDER RESTRICTED | P=0.283N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Casts Protein | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 3/55 (5%) 1/53 (2%) 6/53 (11%) 0/53 (0%) 0/52 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 4/31.53 3/39.63 1/40.59 6/38.91 0/36.61 0/41.53 2/32.74 | |POLY-3 PERCENT (g) | 12.7% 7.6% 2.5% 15.4% 0.0% 0.0% 6.1% | |TERMINAL (d) | 3/15 (20%) 0/25 (0%) 0/26 (0%) 2/22 (9%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 688 516 188 546 --- --- 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.201N P=0.282N P=0.077N P=0.563 P=0.049N* P=0.020N* P=0.514N | |POLY 3 | P=0.118N P=0.376N P=0.111N P=0.506 P=0.042N* P=0.033N* P=0.316N | |POLY 1.5 | P=0.122N P=0.420N P=0.131N P=0.463 P=0.048N* P=0.041N* P=0.316N | |POLY 6 | P=0.118N P=0.317N P=0.091N P=0.556 P=0.037N* P=0.025N* P=0.338N | |LOGISTIC REGRESSION| P=0.135N P=0.387N P=0.166N P=0.487 P=0.035N* P=0.016N* P=0.369N | |COCH-ARM / FISHERS | P=0.136N P=0.479N P=0.181N P=0.371 P=0.059N P=0.061N P=0.339N | |ORDER RESTRICTED | P=0.070N (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/55 (0%) 0/53 (0%) 2/53 (4%) 0/53 (0%) 0/52 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.38 0/38.53 0/39.60 2/37.58 0/36.61 0/41.53 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 1/22 (5%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- 659 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.556N (e) (e) P=0.306 (e) (e) (e) | |POLY 3 | P=0.415N (e) (e) P=0.279 (e) (e) (e) | |POLY 1.5 | P=0.432N (e) (e) P=0.267 (e) (e) (e) | |POLY 6 | P=0.436N (e) (e) P=0.291 (e) (e) (e) | |LOGISTIC REGRESSION| P=0.490N (e) (e) P=0.285 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.469N (e) (e) P=0.248 (e) (e) (e) | |ORDER RESTRICTED | P=0.529N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/55 (0%) 3/53 (6%) 0/53 (0%) 0/53 (0%) 1/52 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.38 0/38.53 3/40.41 0/37.32 0/36.61 1/41.91 2/32.93 | |POLY-3 PERCENT (g) | 0.0% 0.0% 7.4% 0.0% 0.0% 2.4% 6.1% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 651 --- --- 618 555 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.130 (e) P=0.205 (e) (e) P=0.596 P=0.281 | |POLY 3 | P=0.175 (e) P=0.170 (e) (e) P=0.557 P=0.246 | |POLY 1.5 | P=0.173 (e) P=0.150 (e) (e) P=0.536 P=0.247 | |POLY 6 | P=0.183 (e) P=0.198 (e) (e) P=0.579 P=0.234 | |LOGISTIC REGRESSION| P=0.162 (e) P=0.145 (e) (e) P=0.501 P=0.237 | |COCH-ARM / FISHERS | P=0.163 (e) P=0.121 (e) (e) P=0.495 P=0.248 | |ORDER RESTRICTED | P=0.109 (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 2/55 (4%) 1/53 (2%) 1/53 (2%) 1/53 (2%) 1/52 (2%) 0/53 (0%) | |POLY-3 RATE (b) | 2/31.89 2/39.21 1/39.60 1/37.58 1/36.86 1/41.53 0/31.91 | |POLY-3 PERCENT (g) | 6.3% 5.1% 2.5% 2.7% 2.7% 2.4% 0.0% | |TERMINAL (d) | 1/15 (7%) 1/25 (4%) 1/26 (4%) 0/22 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | 574 498 727 (T) 658 659 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.182N P=0.572N P=0.353N P=0.398N P=0.446N P=0.366N P=0.302N | |POLY 3 | P=0.138N P=0.618N P=0.425N P=0.443N P=0.449N P=0.409N P=0.235N | |POLY 1.5 | P=0.134N P=0.645N P=0.450N P=0.458N P=0.467N P=0.441N P=0.231N | |POLY 6 | P=0.159N P=0.580N P=0.396N P=0.429N P=0.434N P=0.377N P=0.255N | |LOGISTIC REGRESSION| P=0.130N P=0.658N P=0.418N P=0.453N P=0.459N P=0.408N P=0.236N | |COCH-ARM / FISHERS | P=0.132N P=0.677N P=0.500N P=0.500N P=0.500N P=0.507N P=0.248N | |ORDER RESTRICTED | P=0.160N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 32/53 (60%) 39/55 (71%) 44/53 (83%) 44/53 (83%) 44/53 (83%) 39/52 (75%) 37/53 (70%) | |POLY-3 RATE (b) | 32/42.76 39/47.07 44/50.44 44/49.02 44/50.35 39/47.55 37/45.03 | |POLY-3 PERCENT (g) | 74.8% 82.9% 87.2% 89.8% 87.4% 82.0% 82.2% | |TERMINAL (d) | 12/15 (80%) 21/25 (84%) 22/26 (85%) 21/22 (96%) 14/16 (88%) 20/23 (87%) 6/7 (86%) | |FIRST INCIDENCE | 126 328 188 385 40 320 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.014 * P=0.241N P=0.416N P=0.438 P=0.224 P=0.183N P=0.068 | |POLY 3 | P=0.479N P=0.230 P=0.085 P=0.033 * P=0.080 P=0.267 P=0.258 | |POLY 1.5 | P=0.425N P=0.187 P=0.037 * P=0.021 * P=0.037 * P=0.186 P=0.258 | |POLY 6 | P=0.486 P=0.297 P=0.181 P=0.044 * P=0.161 P=0.366 P=0.218 | |LOGISTIC REGRESSION| P=0.469N P=0.258 P=0.020 * P=0.024 * P=0.013 * P=0.250 P=0.234 | |COCH-ARM / FISHERS | P=0.479N P=0.171 P=0.008 ** P=0.008 ** P=0.008 ** P=0.082 P=0.208 | |ORDER RESTRICTED | P=0.118 (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 32/53 (60%) 29/55 (53%) 38/53 (72%) 35/53 (66%) 38/53 (72%) 42/52 (81%) 47/53 (89%) | |POLY-3 RATE (b) | 32/43.26 29/42.29 38/44.90 35/44.58 38/44.56 42/46.08 47/48.96 | |POLY-3 PERCENT (g) | 74.0% 68.6% 84.6% 78.5% 85.3% 91.1% 96.0% | |TERMINAL (d) | 11/15 (73%) 20/25 (80%) 26/26 (100%) 21/22 (96%) 14/16 (88%) 22/23 (96%) 7/7 (100%) | |FIRST INCIDENCE | 126 350 376 385 331 554 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.013N* P=0.111N P=0.218N P=0.515 P=0.276N P=0.003 ** | |POLY 3 | P<0.001 ** P=0.366N P=0.131 P=0.387 P=0.116 P=0.014 * P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.363N P=0.124 P=0.375 P=0.096 P=0.011 * P<0.001 ** | |POLY 6 | P<0.001 ** P=0.352N P=0.133 P=0.347 P=0.163 P=0.025 * P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.178N P=0.309 P=0.472 P=0.239 P=0.095 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.272N P=0.153 P=0.344 P=0.153 P=0.018 * P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney: Pelvis | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/55 (2%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 1/52 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 2/32.37 1/38.53 0/39.60 0/37.32 0/36.61 1/41.91 2/33.30 | |POLY-3 PERCENT (g) | 6.2% 2.6% 0.0% 0.0% 0.0% 2.4% 6.0% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 574 727 (T) --- --- --- 618 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.233 P=0.406N P=0.195N P=0.206N P=0.201N P=0.374N P=0.650N | |POLY 3 | P=0.229 P=0.439N P=0.195N P=0.206N P=0.210N P=0.411N P=0.686N | |POLY 1.5 | P=0.241 P=0.458N P=0.208N P=0.213N P=0.218N P=0.442N P=0.680N | |POLY 6 | P=0.224 P=0.413N P=0.181N P=0.202N P=0.204N P=0.381N P=0.681 | |LOGISTIC REGRESSION| P=0.261 P=0.465N P=0.245N P=0.243N P=0.239N P=0.534N P=0.681 | |COCH-ARM / FISHERS | P=0.259 P=0.486N P=0.248N P=0.248N P=0.248N P=0.507N P=0.691N | |ORDER RESTRICTED | P=0.221N (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney: Pelvis | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/55 (0%) 0/53 (0%) 0/53 (0%) 3/53 (6%) 0/52 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 2/32.53 0/38.53 0/39.60 0/37.32 3/38.48 0/41.53 0/31.91 | |POLY-3 PERCENT (g) | 6.2% 0.0% 0.0% 0.0% 7.8% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 541 --- --- --- 301 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.276N P=0.211N P=0.201N P=0.206N P=0.577 P=0.180N P=0.211N | |POLY 3 | P=0.300N P=0.200N P=0.196N P=0.207N P=0.577 P=0.187N P=0.240N | |POLY 1.5 | P=0.295N P=0.212N P=0.209N P=0.213N P=0.551 P=0.204N P=0.233N | |POLY 6 | P=0.338N P=0.185N P=0.182N P=0.203N P=0.598 P=0.172N P=0.263N | |LOGISTIC REGRESSION| P=0.302N P=0.239N P=0.263N P=0.260N P=0.454 P=0.284N P=0.241N | |COCH-ARM / FISHERS | P=0.292N P=0.238N P=0.248N P=0.248N P=0.500 P=0.252N P=0.248N | |ORDER RESTRICTED | P=0.073N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney: Pelvis | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/55 (4%) 2/53 (4%) 2/53 (4%) 0/53 (0%) 0/52 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 0/31.38 2/39.16 2/40.08 2/37.84 0/36.61 0/41.53 1/32.16 | |POLY-3 PERCENT (g) | 0.0% 5.1% 5.0% 5.3% 0.0% 0.0% 3.1% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 1/26 (4%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 524 586 658 --- --- 660 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.438N P=0.307 P=0.331 P=0.316 (e) (e) P=0.460 | |POLY 3 | P=0.288N P=0.289 P=0.295 P=0.280 (e) (e) P=0.505 | |POLY 1.5 | P=0.314N P=0.270 P=0.274 P=0.268 (e) (e) P=0.507 | |POLY 6 | P=0.269N P=0.317 P=0.322 P=0.295 (e) (e) P=0.492 | |LOGISTIC REGRESSION| P=0.365N P=0.257 P=0.270 P=0.269 (e) (e) P=0.497 | |COCH-ARM / FISHERS | P=0.363N P=0.257 P=0.248 P=0.248 (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.449N (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 2/55 (4%) 8/53 (15%) 4/53 (8%) 8/53 (15%) 8/52 (15%) 11/53 (21%) | |POLY-3 RATE (b) | 4/32.45 2/39.16 8/41.11 4/38.52 8/38.99 8/42.50 11/35.55 | |POLY-3 PERCENT (g) | 12.3% 5.1% 19.5% 10.4% 20.5% 18.8% 30.9% | |TERMINAL (d) | 2/15 (13%) 1/25 (4%) 4/26 (15%) 1/22 (5%) 2/16 (13%) 4/23 (17%) 1/7 (14%) | |FIRST INCIDENCE | 554 524 498 500 301 618 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.204N P=0.444 P=0.479N P=0.272 P=0.443 P=0.023 * | |POLY 3 | P=0.004 ** P=0.253N P=0.308 P=0.547N P=0.273 P=0.331 P=0.054 | |POLY 1.5 | P=0.005 ** P=0.279N P=0.258 P=0.573N P=0.237 P=0.270 P=0.054 | |POLY 6 | P=0.003 ** P=0.218N P=0.373 P=0.523N P=0.308 P=0.404 P=0.045 * | |LOGISTIC REGRESSION| P=0.004 ** P=0.281N P=0.269 P=0.585N P=0.210 P=0.323 P=0.050 | |COCH-ARM / FISHERS | P=0.005 ** P=0.322N P=0.179 P=0.642N P=0.179 P=0.170 P=0.046 * | |ORDER RESTRICTED | P=0.011 * (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 8/55 (15%) 4/53 (8%) 1/53 (2%) 1/53 (2%) 2/51 (4%) 2/53 (4%) | |POLY-3 RATE (b) | 3/31.69 8/38.81 4/39.86 1/37.32 1/36.76 2/41.43 2/32.00 | |POLY-3 PERCENT (g) | 9.5% 20.6% 10.0% 2.7% 2.7% 4.8% 6.3% | |TERMINAL (d) | 2/15 (13%) 7/25 (28%) 3/26 (12%) 1/22 (5%) 0/16 (0%) 2/23 (9%) 1/7 (14%) | |FIRST INCIDENCE | 644 652 659 727 (T) 688 727 (T) 704 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.273N P=0.316 P=0.548N P=0.193N P=0.256N P=0.312N P=0.594 | |POLY 3 | P=0.071N P=0.169 P=0.624 P=0.247N P=0.252N P=0.380N P=0.495N | |POLY 1.5 | P=0.078N P=0.142 P=0.581 P=0.262N P=0.270N P=0.425N P=0.487N | |POLY 6 | P=0.068N P=0.216 P=0.636N P=0.235N P=0.237N P=0.337N P=0.535N | |LOGISTIC REGRESSION| P=0.141N P=0.264 P=0.616N P=0.216N P=0.232N P=0.291N P=0.625N | |COCH-ARM / FISHERS | P=0.092N P=0.113 P=0.500 P=0.309N P=0.309N P=0.518N P=0.500N | |ORDER RESTRICTED | P=0.093N (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/53 (13%) 10/55 (18%) 10/53 (19%) 13/53 (25%) 4/53 (8%) 5/51 (10%) 5/53 (9%) | |POLY-3 RATE (b) | 7/32.51 10/39.34 10/40.14 13/39.28 4/36.97 5/41.49 5/32.77 | |POLY-3 PERCENT (g) | 21.5% 25.4% 24.9% 33.1% 10.8% 12.1% 15.3% | |TERMINAL (d) | 3/15 (20%) 7/25 (28%) 8/26 (31%) 9/22 (41%) 1/16 (6%) 4/23 (17%) 2/7 (29%) | |FIRST INCIDENCE | 541 574 651 454 658 714 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.316N P=0.529N P=0.489N P=0.322 P=0.182N P=0.129N P=0.545 | |POLY 3 | P=0.036N* P=0.457 P=0.476 P=0.201 P=0.184N P=0.219N P=0.367N | |POLY 1.5 | P=0.037N* P=0.401 P=0.412 P=0.171 P=0.209N P=0.274N P=0.357N | |POLY 6 | P=0.045N* P=0.538 P=0.550 P=0.229 P=0.166N P=0.173N P=0.427N | |LOGISTIC REGRESSION| P=0.067N P=0.538 P=0.589 P=0.207 P=0.157N P=0.144N P=0.416N | |COCH-ARM / FISHERS | P=0.049N* P=0.329 P=0.299 P=0.107 P=0.263N P=0.408N P=0.380N | |ORDER RESTRICTED | P=0.165N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Cholangiofibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 1/55 (2%) 1/53 (2%) 1/53 (2%) 3/53 (6%) 13/51 (25%) 22/53 (42%) | |POLY-3 RATE (b) | 0/31.38 1/38.53 1/39.60 1/37.32 3/37.59 13/41.80 22/38.60 | |POLY-3 PERCENT (g) | 0.0% 2.6% 2.5% 2.7% 8.0% 31.1% 57.0% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 1/26 (4%) 1/22 (5%) 0/16 (0%) 10/23 (44%) 3/7 (43%) | |FIRST INCIDENCE | --- 727 (T) 727 (T) 727 (T) 607 651 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.602 P=0.610 P=0.576 P=0.182 P=0.002 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.541 P=0.546 P=0.534 P=0.153 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.527 P=0.530 P=0.525 P=0.140 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.561 P=0.565 P=0.543 P=0.169 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.602 P=0.610 P=0.576 P=0.133 P=0.002 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.509 P=0.500 P=0.500 P=0.121 P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/55 (2%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/51 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 2/31.38 1/39.30 0/39.60 0/37.32 0/36.61 0/41.43 0/31.91 | |POLY-3 PERCENT (g) | 6.4% 2.5% 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/15 (13%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 727 (T) 448 --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.139N P=0.373N P=0.127N P=0.157N P=0.222N P=0.149N P=0.416N | |POLY 3 | P=0.117N P=0.422N P=0.189N P=0.200N P=0.203N P=0.182N P=0.232N | |POLY 1.5 | P=0.122N P=0.449N P=0.205N P=0.210N P=0.215N P=0.201N P=0.229N | |POLY 6 | P=0.125N P=0.385N P=0.171N P=0.190N P=0.193N P=0.163N P=0.248N | |LOGISTIC REGRESSION| P=0.122N P=0.461N (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.124N P=0.486N P=0.248N P=0.248N P=0.248N P=0.257N P=0.248N | |ORDER RESTRICTED | P=0.019N* (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/55 (0%) 0/53 (0%) 0/53 (0%) 1/53 (2%) 1/51 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.38 0/38.53 0/39.60 0/37.32 1/36.61 1/41.43 2/32.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 2.7% 2.4% 6.3% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 1/16 (6%) 1/23 (4%) 1/7 (14%) | |FIRST INCIDENCE | --- --- --- --- 727 (T) 727 (T) 704 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) P=0.513 P=0.585 P=0.105 | |POLY 3 | P=0.013 * (e) (e) (e) P=0.531 P=0.554 P=0.240 | |POLY 1.5 | P=0.015 * (e) (e) (e) P=0.520 P=0.534 P=0.243 | |POLY 6 | P=0.013 * (e) (e) (e) P=0.540 P=0.576 P=0.222 | |LOGISTIC REGRESSION| P=0.002 ** (e) (e) (e) P=0.513 P=0.585 P=0.148 | |COCH-ARM / FISHERS | P=0.017 * (e) (e) (e) P=0.500 P=0.490 P=0.248 | |ORDER RESTRICTED | P=0.048 * (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/53 (21%) 10/55 (18%) 13/53 (25%) 21/53 (40%) 17/53 (32%) 24/51 (47%) 17/53 (32%) | |POLY-3 RATE (b) | 11/34.24 10/39.49 13/42.24 21/43.22 17/39.64 24/47.33 17/41.05 | |POLY-3 PERCENT (g) | 32.1% 25.3% 30.8% 48.6% 42.9% 50.7% 41.4% | |TERMINAL (d) | 5/15 (33%) 6/25 (24%) 5/26 (19%) 7/22 (32%) 5/16 (31%) 7/23 (30%) 1/7 (14%) | |FIRST INCIDENCE | 405 524 509 385 531 440 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.148N P=0.328N P=0.186 P=0.301 P=0.194 P=0.096 | |POLY 3 | P=0.057 P=0.347N P=0.548N P=0.103 P=0.233 P=0.073 P=0.272 | |POLY 1.5 | P=0.046 * P=0.393N P=0.565 P=0.068 P=0.191 P=0.028 * P=0.226 | |POLY 6 | P=0.050 P=0.285N P=0.452N P=0.165 P=0.287 P=0.171 P=0.291 | |LOGISTIC REGRESSION| P=0.021 * P=0.312N P=0.581 P=0.056 P=0.236 P=0.013 * P=0.135 | |COCH-ARM / FISHERS | P=0.023 * P=0.462N P=0.408 P=0.028 * P=0.135 P=0.004 ** P=0.135 | |ORDER RESTRICTED | P=0.100 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Fatty Change Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 7/55 (13%) 14/53 (26%) 22/53 (42%) 30/53 (57%) 45/51 (88%) 47/53 (89%) | |POLY-3 RATE (b) | 5/33.58 7/40.50 14/43.35 22/41.83 30/43.70 45/48.97 47/47.72 | |POLY-3 PERCENT (g) | 14.9% 17.3% 32.3% 52.6% 68.7% 91.9% 98.5% | |TERMINAL (d) | 2/15 (13%) 2/25 (8%) 6/26 (23%) 11/22 (50%) 10/16 (63%) 21/23 (91%) 7/7 (100%) | |FIRST INCIDENCE | 126 448 376 481 163 440 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.614 P=0.142 P=0.005 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.515 P=0.066 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.462 P=0.042 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.594 P=0.111 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.403 P=0.020 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.407 P=0.020 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Fatty Change Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 6/55 (11%) 8/53 (15%) 6/53 (11%) 3/53 (6%) 2/51 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 2/32.02 6/38.55 8/40.14 6/37.58 3/36.91 2/42.21 0/31.91 | |POLY-3 PERCENT (g) | 6.3% 15.6% 19.9% 16.0% 8.1% 4.7% 0.0% | |TERMINAL (d) | 1/15 (7%) 5/25 (20%) 5/26 (19%) 5/22 (23%) 2/16 (13%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | 519 722 653 660 645 440 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.032N* P=0.324 P=0.189 P=0.256 P=0.554 P=0.576N P=0.302N | |POLY 3 | P=0.005N** P=0.197 P=0.091 P=0.186 P=0.565 P=0.590N P=0.236N | |POLY 1.5 | P=0.005N** P=0.174 P=0.073 P=0.172 P=0.543 P=0.630N P=0.232N | |POLY 6 | P=0.006N** P=0.235 P=0.120 P=0.198 P=0.585 P=0.548N P=0.256N | |LOGISTIC REGRESSION| P=0.009N** P=0.250 P=0.110 P=0.209 P=0.568 P=0.673 P=0.234N | |COCH-ARM / FISHERS | P=0.008N** P=0.147 P=0.046 * P=0.135 P=0.500 P=0.676 P=0.248N | |ORDER RESTRICTED | P=0.053N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Hepatocyte, Multinucleate | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/55 (4%) 10/53 (19%) 14/53 (26%) 19/53 (36%) 46/51 (90%) 49/53 (92%) | |POLY-3 RATE (b) | 0/31.38 2/38.53 10/40.61 14/40.28 19/39.58 46/47.56 49/50.73 | |POLY-3 PERCENT (g) | 0.0% 5.2% 24.6% 34.8% 48.0% 96.7% 96.6% | |TERMINAL (d) | 0/15 (0%) 2/25 (8%) 7/26 (27%) 8/22 (36%) 9/16 (56%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | --- 727 (T) 509 481 331 440 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.356 P=0.012 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.285 P=0.003 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.268 P=0.002 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.310 P=0.006 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.356 P=0.005 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.257 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/55 (0%) 0/53 (0%) 1/53 (2%) 3/53 (6%) 26/51 (51%) 39/53 (74%) | |POLY-3 RATE (b) | 0/31.38 0/38.53 0/39.60 1/37.32 3/36.86 26/43.63 39/42.89 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.7% 8.1% 59.6% 90.9% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 1/22 (5%) 1/16 (6%) 18/23 (78%) 7/7 (100%) | |FIRST INCIDENCE | --- --- --- 727 (T) 680 535 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P=0.576 P=0.163 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P=0.534 P=0.148 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P=0.525 P=0.137 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P=0.543 P=0.160 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.576 P=0.160 P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.500 P=0.121 P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 36/53 (68%) 40/55 (73%) 49/53 (92%) 50/53 (94%) 51/53 (96%) 51/51 (100%) 51/53 (96%) | |POLY-3 RATE (b) | 36/42.80 40/46.70 49/50.26 50/50.96 51/51.40 51/51.00 51/52.15 | |POLY-3 PERCENT (g) | 84.1% 85.7% 97.5% 98.1% 99.2% 100.0% 97.8% | |TERMINAL (d) | 15/15 (100%) 21/25 (84%) 25/26 (96%) 22/22 (100%) 16/16 (100%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | 176 253 188 385 40 185 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.082N P=0.334N P=0.405 P=0.148 P=0.428N P=0.002 ** | |POLY 3 | P<0.001 ** P=0.543 P=0.008 ** P=0.004 ** P<0.001 ** P<0.001 ** P=0.004 ** | |POLY 1.5 | P<0.001 ** P=0.427 P=0.002 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P=0.006 ** P=0.527N P=0.061 P=0.020 * P=0.006 ** P=0.004 ** P=0.019 * | |LOGISTIC REGRESSION| P<0.001 ** P=0.548 P=0.009 ** P=0.003 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.369 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 21/53 (40%) 24/55 (44%) 32/53 (60%) 32/53 (60%) 30/53 (57%) 29/51 (57%) 9/53 (17%) | |POLY-3 RATE (b) | 21/34.34 24/40.37 32/42.94 32/43.91 30/42.01 29/43.57 9/34.56 | |POLY-3 PERCENT (g) | 61.2% 59.5% 74.5% 72.9% 71.4% 66.6% 26.0% | |TERMINAL (d) | 12/15 (80%) 19/25 (76%) 22/26 (85%) 19/22 (86%) 15/16 (94%) 19/23 (83%) 3/7 (43%) | |FIRST INCIDENCE | 541 546 541 385 454 574 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.255N P=0.087N P=0.449N P=0.349 P=0.201 P=0.343N P=0.137N | |POLY 3 | P<0.001N** P=0.537N P=0.131 P=0.170 P=0.219 P=0.392 P<0.001N** | |POLY 1.5 | P<0.001N** P=0.553 P=0.071 P=0.099 P=0.130 P=0.230 P=0.002N** | |POLY 6 | P<0.001N** P=0.398N P=0.257 P=0.261 P=0.351 P=0.585 P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P=0.313N P=0.257 P=0.104 P=0.198 P=0.480N P=0.005N** | |COCH-ARM / FISHERS | P<0.001N** P=0.410 P=0.026 * P=0.026 * P=0.060 P=0.059 P=0.008N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 2/55 (4%) 5/53 (9%) 8/53 (15%) 11/53 (21%) 15/51 (29%) 17/53 (32%) | |POLY-3 RATE (b) | 4/34.03 2/39.44 5/42.49 8/41.14 11/39.49 15/44.94 17/38.49 | |POLY-3 PERCENT (g) | 11.8% 5.1% 11.8% 19.5% 27.9% 33.4% 44.2% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 3/16 (19%) 6/23 (26%) 1/7 (14%) | |FIRST INCIDENCE | 176 356 300 481 403 185 530 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.242N P=0.624 P=0.294 P=0.112 P=0.064 P=0.004 ** | |POLY 3 | P<0.001 ** P=0.269N P=0.637 P=0.278 P=0.075 P=0.024 * P=0.002 ** | |POLY 1.5 | P<0.001 ** P=0.291N P=0.589 P=0.243 P=0.061 P=0.013 * P<0.001 ** | |POLY 6 | P<0.001 ** P=0.240N P=0.583N P=0.320 P=0.093 P=0.045 * P=0.002 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.373N P=0.320 P=0.101 P=0.047 * P=0.002 ** P=0.002 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.322N P=0.500 P=0.179 P=0.046 * P=0.004 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 11/55 (20%) 41/53 (77%) 39/53 (74%) 48/53 (91%) 51/51 (100%) 48/53 (91%) | |POLY-3 RATE (b) | 1/32.06 11/39.46 41/47.21 39/44.38 48/49.35 51/51.00 48/48.68 | |POLY-3 PERCENT (g) | 3.1% 27.9% 86.9% 87.9% 97.3% 100.0% 98.6% | |TERMINAL (d) | 0/15 (0%) 7/25 (28%) 23/26 (89%) 21/22 (96%) 15/16 (94%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | 496 572 328 405 247 185 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.024 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.005 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.004 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.009 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.008 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Toxic Hepatopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 6/55 (11%) 22/53 (42%) 27/53 (51%) 39/53 (74%) 51/51 (100%) 49/53 (92%) | |POLY-3 RATE (b) | 0/31.38 6/38.95 22/41.68 27/41.02 39/43.36 51/51.00 49/49.10 | |POLY-3 PERCENT (g) | 0.0% 15.4% 52.8% 65.8% 90.0% 100.0% 99.8% | |TERMINAL (d) | 0/15 (0%) 3/25 (12%) 15/26 (58%) 18/22 (82%) 15/16 (94%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | --- 652 328 454 541 185 243 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.068 P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.029 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.023 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.040 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.042 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.015 * P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 6/55 (11%) 0/53 (0%) 2/53 (4%) 3/53 (6%) 8/51 (16%) 12/53 (23%) | |POLY-3 RATE (b) | 3/31.38 6/38.56 0/39.60 2/37.58 3/36.99 8/41.43 12/35.10 | |POLY-3 PERCENT (g) | 9.6% 15.6% 0.0% 5.3% 8.1% 19.3% 34.2% | |TERMINAL (d) | 3/15 (20%) 5/25 (20%) 0/26 (0%) 1/22 (5%) 2/16 (13%) 8/23 (35%) 3/7 (43%) | |FIRST INCIDENCE | 727 (T) 720 --- 659 618 727 (T) 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.545 P=0.042N* P=0.343N P=0.618N P=0.272 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.350 P=0.082N P=0.418N P=0.586N P=0.209 P=0.014 * | |POLY 1.5 | P<0.001 ** P=0.311 P=0.094N P=0.441N P=0.614N P=0.160 P=0.014 * | |POLY 6 | P<0.001 ** P=0.412 P=0.069N P=0.394N P=0.557N P=0.270 P=0.010 * | |LOGISTIC REGRESSION| P<0.001 ** P=0.568 (e) P=0.373N P=0.556N P=0.272 P=0.012 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.263 P=0.121N P=0.500N P=0.661N P=0.089 P=0.012 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 4/55 (7%) 3/53 (6%) 2/53 (4%) 1/53 (2%) 4/51 (8%) 5/53 (9%) | |POLY-3 RATE (b) | 4/32.23 4/38.64 3/39.75 2/38.02 1/36.86 4/42.20 5/33.91 | |POLY-3 PERCENT (g) | 12.4% 10.4% 7.6% 5.3% 2.7% 9.5% 14.8% | |TERMINAL (d) | 3/15 (20%) 3/25 (12%) 1/26 (4%) 0/22 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | 391 700 709 600 658 535 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.082 P=0.382N P=0.253N P=0.223N P=0.148N P=0.408N P=0.359 | |POLY 3 | P=0.240 P=0.541N P=0.386N P=0.262N P=0.137N P=0.489N P=0.533 | |POLY 1.5 | P=0.248 P=0.577N P=0.426N P=0.283N P=0.152N P=0.550N P=0.528 | |POLY 6 | P=0.226 P=0.485N P=0.338N P=0.239N P=0.124N P=0.423N P=0.516 | |LOGISTIC REGRESSION| P=0.234 P=0.512N P=0.378N P=0.289N P=0.149N P=0.564N P=0.512 | |COCH-ARM / FISHERS | P=0.252 P=0.621N P=0.500N P=0.339N P=0.181N P=0.620 P=0.500 | |ORDER RESTRICTED | P=0.305 (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 7/55 (13%) 7/53 (13%) 13/53 (25%) 14/53 (26%) 45/51 (88%) 45/53 (85%) | |POLY-3 RATE (b) | 3/32.67 7/39.97 7/39.86 13/41.26 14/39.77 45/47.42 45/45.98 | |POLY-3 PERCENT (g) | 9.2% 17.5% 17.6% 31.5% 35.2% 94.9% 97.9% | |TERMINAL (d) | 1/15 (7%) 4/25 (16%) 6/26 (23%) 5/22 (23%) 5/16 (31%) 22/23 (96%) 7/7 (100%) | |FIRST INCIDENCE | 496 434 659 405 328 535 394 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.337 P=0.392 P=0.036 * P=0.015 * P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.248 P=0.246 P=0.019 * P=0.008 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.215 P=0.215 P=0.013 * P=0.006 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.298 P=0.288 P=0.027 * P=0.011 * P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.205 P=0.264 P=0.009 ** P=0.006 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.176 P=0.160 P=0.006 ** P=0.003 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 1/55 (2%) 1/53 (2%) 0/53 (0%) 1/53 (2%) 1/51 (2%) 7/53 (13%) | |POLY-3 RATE (b) | 3/33.04 1/38.64 1/40.21 0/37.32 1/36.68 1/41.62 7/34.41 | |POLY-3 PERCENT (g) | 9.1% 2.6% 2.5% 0.0% 2.7% 2.4% 20.3% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 354 700 533 --- 709 678 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.210N P=0.233N P=0.094N P=0.256N P=0.191N P=0.129 | |POLY 3 | P=0.002 ** P=0.250N P=0.238N P=0.097N P=0.267N P=0.228N P=0.165 | |POLY 1.5 | P=0.002 ** P=0.267N P=0.260N P=0.102N P=0.279N P=0.256N P=0.169 | |POLY 6 | P=0.002 ** P=0.224N P=0.213N P=0.093N P=0.257N P=0.201N P=0.145 | |LOGISTIC REGRESSION| P=0.002 ** P=0.302N P=0.375N P=0.151N P=0.316N P=0.396N P=0.162 | |COCH-ARM / FISHERS | P=0.002 ** P=0.295N P=0.309N P=0.121N P=0.309N P=0.324N P=0.160 | |ORDER RESTRICTED | P=0.002 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 23/55 (42%) 32/53 (60%) 36/53 (68%) 42/53 (79%) 50/51 (98%) 49/53 (92%) | |POLY-3 RATE (b) | 0/31.38 23/43.50 32/45.22 36/46.82 42/46.52 50/50.61 49/49.44 | |POLY-3 PERCENT (g) | 0.0% 52.9% 70.8% 76.9% 90.3% 98.8% 99.1% | |TERMINAL (d) | 0/15 (0%) 10/25 (40%) 18/26 (69%) 17/22 (77%) 15/16 (94%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | --- 448 188 385 328 185 243 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** 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 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** 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 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** 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 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Oval Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 1/55 (2%) 6/53 (11%) 7/53 (13%) 10/53 (19%) 38/51 (75%) 40/53 (75%) | |POLY-3 RATE (b) | 0/31.38 1/38.56 6/39.60 7/37.32 10/37.11 38/44.37 40/43.32 | |POLY-3 PERCENT (g) | 0.0% 2.6% 15.2% 18.8% 27.0% 85.6% 92.3% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 6/26 (23%) 7/22 (32%) 6/16 (38%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | --- 720 727 (T) 727 (T) 630 535 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.624 P=0.062 P=0.024 * P=0.003 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.541 P=0.031 * P=0.013 * P=0.002 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.527 P=0.025 * P=0.012 * P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.561 P=0.041 * P=0.015 * P=0.002 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.596 P=0.062 P=0.024 * P=0.003 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.509 P=0.013 * P=0.006 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Portal | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/55 (0%) 0/53 (0%) 0/53 (0%) 2/53 (4%) 1/51 (2%) 10/53 (19%) | |POLY-3 RATE (b) | 0/31.38 0/38.53 0/39.60 0/37.32 2/37.17 1/41.55 10/34.71 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 5.4% 2.4% 28.8% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 1/7 (14%) | |FIRST INCIDENCE | --- --- --- --- 618 699 574 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) P=0.306 P=0.626 P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) (e) P=0.276 P=0.555 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) (e) P=0.261 P=0.534 P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) (e) P=0.291 P=0.577 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) P=0.260 P=0.579 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P=0.248 P=0.490 P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 41/53 (77%) 49/55 (89%) 45/53 (85%) 48/53 (91%) 45/53 (85%) 49/51 (96%) 42/51 (82%) | |POLY-3 RATE (b) | 41/47.06 49/51.17 45/47.89 48/49.78 45/46.48 49/49.11 42/44.15 | |POLY-3 PERCENT (g) | 87.1% 95.8% 94.0% 96.4% 96.8% 99.8% 95.1% | |TERMINAL (d) | 12/15 (80%) 23/25 (92%) 26/26 (100%) 21/22 (96%) 15/16 (94%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | 201 253 328 385 454 320 394 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.009 ** P=0.201N P=0.049N* P=0.335N P=0.406N P=0.118N P=0.164 | |POLY 3 | P=0.093 P=0.099 P=0.185 P=0.069 P=0.064 P=0.007 ** P=0.133 | |POLY 1.5 | P=0.132 P=0.062 P=0.192 P=0.058 P=0.070 P=0.004 ** P=0.156 | |POLY 6 | P=0.077 P=0.182 P=0.187 P=0.097 P=0.100 P=0.019 * P=0.128 | |LOGISTIC REGRESSION| P=0.504 P=0.128 P=0.479 P=0.144 P=0.410 P=0.037 * P=0.445 | |COCH-ARM / FISHERS | P=0.411 P=0.084 P=0.229 P=0.055 P=0.229 P=0.005 ** P=0.349 | |ORDER RESTRICTED | P=0.006 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 3/55 (5%) 0/53 (0%) 1/53 (2%) 1/53 (2%) 0/51 (0%) 2/51 (4%) | |POLY-3 RATE (b) | 5/32.66 3/39.74 0/39.60 1/37.78 1/37.61 0/41.13 2/31.84 | |POLY-3 PERCENT (g) | 15.3% 7.6% 0.0% 2.7% 2.7% 0.0% 6.3% | |TERMINAL (d) | 2/15 (13%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 309 356 --- 592 40 --- 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.289N P=0.179N P=0.010N* P=0.057N P=0.086N P=0.011N* P=0.375N | |POLY 3 | P=0.215N P=0.252N P=0.017N* P=0.069N P=0.069N P=0.015N* P=0.220N | |POLY 1.5 | P=0.223N P=0.286N P=0.021N* P=0.077N P=0.079N P=0.020N* P=0.219N | |POLY 6 | P=0.207N P=0.207N P=0.013N* P=0.061N P=0.062N P=0.011N* P=0.244N | |LOGISTIC REGRESSION| P=0.238N P=0.321N P=0.026N* P=0.088N P=0.121N P=0.027N* P=0.225N | |COCH-ARM / FISHERS | P=0.231N P=0.337N P=0.028N* P=0.103N P=0.103N P=0.031N* P=0.235N | |ORDER RESTRICTED | P=0.011N* (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 0/55 (0%) 2/53 (4%) 0/53 (0%) 0/53 (0%) 0/51 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 3/32.04 0/38.53 2/39.67 0/37.32 0/36.61 0/41.13 0/30.95 | |POLY-3 PERCENT (g) | 9.4% 0.0% 5.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/15 (7%) 0/25 (0%) 1/26 (4%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 611 --- 709 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.078N P=0.066N P=0.300N P=0.085N P=0.097N P=0.057N P=0.179N | |POLY 3 | P=0.061N P=0.088N P=0.403N P=0.092N P=0.095N P=0.080N P=0.122N | |POLY 1.5 | P=0.064N P=0.097N P=0.435N P=0.098N P=0.102N P=0.094N P=0.120N | |POLY 6 | P=0.065N P=0.076N P=0.368N P=0.088N P=0.090N P=0.069N P=0.137N | |LOGISTIC REGRESSION| P=0.065N P=0.088N P=0.374N P=0.092N P=0.095N P=0.082N P=0.127N | |COCH-ARM / FISHERS | P=0.069N P=0.115N P=0.500N P=0.121N P=0.121N P=0.129N P=0.129N | |ORDER RESTRICTED | P=0.007N** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 0/55 (0%) 1/53 (2%) 2/53 (4%) 3/53 (6%) 9/51 (18%) 4/51 (8%) | |POLY-3 RATE (b) | 1/31.53 0/38.53 1/39.60 2/37.32 3/37.05 9/42.85 4/31.72 | |POLY-3 PERCENT (g) | 3.2% 0.0% 2.5% 5.4% 8.1% 21.0% 12.6% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/26 (4%) 2/22 (9%) 2/16 (13%) 2/23 (9%) 2/7 (29%) | |FIRST INCIDENCE | 688 --- 727 (T) 727 (T) 599 573 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.405N P=0.642N P=0.616 P=0.365 P=0.066 P=0.092 | |POLY 3 | P<0.001 ** P=0.460N P=0.708N P=0.559 P=0.364 P=0.030 * P=0.175 | |POLY 1.5 | P<0.001 ** P=0.474N P=0.727N P=0.543 P=0.343 P=0.018 * P=0.177 | |POLY 6 | P<0.001 ** P=0.441N P=0.685N P=0.572 P=0.384 P=0.051 P=0.157 | |LOGISTIC REGRESSION| P<0.001 ** P=0.448N P=0.677N P=0.598 P=0.372 P=0.021 * P=0.153 | |COCH-ARM / FISHERS | P=0.002 ** P=0.491N P=0.752N P=0.500 P=0.309 P=0.007 ** P=0.170 | |ORDER RESTRICTED | P=0.016 * (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/55 (4%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 1/51 (2%) 0/51 (0%) | |POLY-3 RATE (b) | 0/31.38 2/38.67 0/39.60 0/37.32 0/36.61 1/41.64 0/30.95 | |POLY-3 PERCENT (g) | 0.0% 5.2% 0.0% 0.0% 0.0% 2.4% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 700 --- --- --- 573 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.509N P=0.374 (e) (e) (e) P=0.566 (e) | |POLY 3 | P=0.435N P=0.286 (e) (e) (e) P=0.555 (e) | |POLY 1.5 | P=0.444N P=0.268 (e) (e) (e) P=0.534 (e) | |POLY 6 | P=0.460N P=0.312 (e) (e) (e) P=0.578 (e) | |LOGISTIC REGRESSION| P=0.455N P=0.322 (e) (e) (e) P=0.461 (e) | |COCH-ARM / FISHERS | P=0.452N P=0.257 (e) (e) (e) P=0.490 (e) | |ORDER RESTRICTED | P=0.307N (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/53 (23%) 1/55 (2%) 0/53 (0%) 1/53 (2%) 2/53 (4%) 0/51 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 12/32.58 1/38.75 0/39.60 1/37.32 2/37.28 0/41.13 0/30.95 | |POLY-3 PERCENT (g) | 36.8% 2.6% 0.0% 2.7% 5.4% 0.0% 0.0% | |TERMINAL (d) | 7/15 (47%) 0/25 (0%) 0/26 (0%) 1/22 (5%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 600 671 --- 727 (T) 607 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002N** P<0.001N** P<0.001N** P<0.001N** P=0.002N** P<0.001N** P=0.005N** | |POLY 3 | P<0.001N** P<0.001N** P<0.001N** 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** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P<0.001N** P<0.001N** P<0.001N** 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** P<0.001N** P<0.001N** P<0.001N** | |COCH-ARM / FISHERS | P=0.002N** P<0.001N** P<0.001N** P<0.001N** P=0.004N** P<0.001N** P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG 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%) 39/53 (74%) 47/51 (92%) 40/51 (78%) | |POLY-3 RATE (b) | 0/31.38 29/41.27 34/43.69 41/45.19 39/44.76 47/48.24 40/43.59 | |POLY-3 PERCENT (g) | 0.0% 70.3% 77.8% 90.7% 87.1% 97.4% 91.8% | |TERMINAL (d) | 0/15 (0%) 19/25 (76%) 22/26 (85%) 21/22 (96%) 15/16 (94%) 23/23 (100%) 6/7 (86%) | |FIRST INCIDENCE | --- 516 541 405 454 320 394 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** 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 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** 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 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** 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 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung: Serosa | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/55 (0%) 2/53 (4%) 0/53 (0%) 0/53 (0%) 0/51 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 0/31.38 0/38.53 2/39.88 0/37.32 0/36.61 0/41.13 0/30.95 | |POLY-3 PERCENT (g) | 0.0% 0.0% 5.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/26 (4%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 651 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.413N (e) P=0.358 (e) (e) (e) (e) | |POLY 3 | P=0.267N (e) P=0.294 (e) (e) (e) (e) | |POLY 1.5 | P=0.298N (e) P=0.273 (e) (e) (e) (e) | |POLY 6 | P=0.261N (e) P=0.320 (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.356N (e) P=0.300 (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.351N (e) P=0.248 (e) (e) (e) (e) | |ORDER RESTRICTED | P=0.421N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung: Serosa | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/55 (0%) 0/53 (0%) 1/53 (2%) 1/53 (2%) 0/51 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 2/32.84 0/38.53 0/39.60 1/38.32 1/37.59 0/41.13 0/30.95 | |POLY-3 PERCENT (g) | 6.1% 0.0% 0.0% 2.6% 2.7% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 126 --- --- 124 163 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.210N P=0.218N P=0.215N P=0.482N P=0.476N P=0.204N P=0.228N | |POLY 3 | P=0.216N P=0.202N P=0.197N P=0.446N P=0.453N P=0.191N P=0.249N | |POLY 1.5 | P=0.216N P=0.214N P=0.211N P=0.459N P=0.468N P=0.209N P=0.244N | |POLY 6 | P=0.238N P=0.186N P=0.182N P=0.436N P=0.441N P=0.174N P=0.268N | |LOGISTIC REGRESSION| P=0.225N P=0.267N P=0.371N P=0.703 P=0.584N P=0.449N P=0.270N | |COCH-ARM / FISHERS | P=0.220N P=0.238N P=0.248N P=0.500N P=0.500N P=0.257N P=0.257N | |ORDER RESTRICTED | P=0.053N (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 1/53 (2%) 4/51 (8%) 4/51 (8%) 4/52 (8%) 4/51 (8%) 3/51 (6%) | |POLY-3 RATE (b) | 1/31.47 1/37.64 4/38.08 4/36.51 4/35.81 4/41.14 3/30.95 | |POLY-3 PERCENT (g) | 3.2% 2.7% 10.5% 11.0% 11.2% 9.7% 9.7% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 4/25 (16%) 4/22 (18%) 3/16 (19%) 3/23 (13%) 3/7 (43%) | |FIRST INCIDENCE | 660 722 727 (T) 727 (T) 722 722 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.022 * P=0.658N P=0.344 P=0.293 P=0.215 P=0.339 P=0.115 | |POLY 3 | P=0.234 P=0.720N P=0.240 P=0.224 P=0.217 P=0.270 P=0.296 | |POLY 1.5 | P=0.261 P=0.736N P=0.215 P=0.210 P=0.204 P=0.235 P=0.304 | |POLY 6 | P=0.188 P=0.695N P=0.272 P=0.237 P=0.228 P=0.311 P=0.265 | |LOGISTIC REGRESSION| P=0.057 P=0.709N P=0.309 P=0.264 P=0.243 P=0.345 P=0.188 | |COCH-ARM / FISHERS | P=0.273 P=0.748N P=0.175 P=0.175 P=0.181 P=0.175 P=0.301 | |ORDER RESTRICTED | P=0.291 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 18/52 (35%) 24/53 (45%) 31/51 (61%) 21/51 (41%) 29/52 (56%) 11/51 (22%) 15/51 (29%) | |POLY-3 RATE (b) | 18/36.75 24/45.45 31/41.45 21/38.38 29/42.17 11/42.99 15/36.60 | |POLY-3 PERCENT (g) | 49.0% 52.8% 74.8% 54.7% 68.8% 25.6% 41.0% | |TERMINAL (d) | 8/15 (53%) 9/25 (36%) 21/25 (84%) 16/22 (73%) 12/16 (75%) 5/23 (22%) 1/7 (14%) | |FIRST INCIDENCE | 222 202 531 496 163 320 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.249N P=0.485N P=0.365 P=0.348N P=0.127 P=0.009N** P=0.552 | |POLY 3 | P<0.001N** P=0.450 P=0.010 * P=0.388 P=0.046 * P=0.023N* P=0.318N | |POLY 1.5 | P=0.002N** P=0.328 P=0.007 ** P=0.389 P=0.035 * P=0.038N* P=0.327N | |POLY 6 | P=0.002N** P=0.571N P=0.017 * P=0.369 P=0.065 P=0.013N* P=0.329N | |LOGISTIC REGRESSION| P=0.004N** P=0.205 P=0.034 * P=0.544 P=0.043 * P=0.059N P=0.338N | |COCH-ARM / FISHERS | P=0.005N** P=0.180 P=0.007 ** P=0.315 P=0.024 * P=0.105N P=0.362N | |ORDER RESTRICTED | P=0.009N** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 1/53 (2%) 1/51 (2%) 1/51 (2%) 2/52 (4%) 0/51 (0%) 1/51 (2%) | |POLY-3 RATE (b) | 0/31.21 1/37.90 1/38.68 1/37.34 2/36.75 0/41.11 1/30.95 | |POLY-3 PERCENT (g) | 0.0% 2.6% 2.6% 2.7% 5.4% 0.0% 3.2% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/25 (0%) 0/22 (0%) 1/16 (6%) 0/23 (0%) 1/7 (14%) | |FIRST INCIDENCE | --- 652 533 405 247 --- 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.500 P=0.578 P=0.535 P=0.539 P=0.254 (e) P=0.348 | |POLY 3 | P=0.579 P=0.538 P=0.542 P=0.536 P=0.274 (e) P=0.498 | |POLY 1.5 | P=0.584 P=0.523 P=0.526 P=0.524 P=0.262 (e) P=0.501 | |POLY 6 | P=0.585 P=0.561 P=0.562 P=0.547 P=0.287 (e) P=0.484 | |LOGISTIC REGRESSION| P=0.571 P=0.525 P=0.462 P=0.388 P=0.211 (e) P=0.348 | |COCH-ARM / FISHERS | P=0.575 P=0.505 P=0.495 P=0.495 P=0.248 (e) P=0.495 | |ORDER RESTRICTED | P=0.412 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 3/54 (6%) 0/52 (0%) 1/52 (2%) 1/53 (2%) 0/51 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 2/31.83 3/39.51 0/38.60 1/36.90 1/36.68 0/41.43 2/33.24 | |POLY-3 PERCENT (g) | 6.3% 7.6% 0.0% 2.7% 2.7% 0.0% 6.0% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 0/25 (0%) 0/21 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 618 498 --- 546 709 --- 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.575N P=0.642 P=0.150N P=0.427N P=0.411N P=0.137N P=0.653 | |POLY 3 | P=0.460N P=0.598 P=0.196N P=0.448N P=0.450N P=0.184N P=0.681N | |POLY 1.5 | P=0.481N P=0.562 P=0.210N P=0.462N P=0.466N P=0.202N P=0.677N | |POLY 6 | P=0.438N P=0.644 P=0.181N P=0.437N P=0.438N P=0.167N P=0.692 | |LOGISTIC REGRESSION| P=0.508N P=0.539 P=0.200N P=0.481N P=0.441N P=0.192N P=0.688N | |COCH-ARM / FISHERS | P=0.509N P=0.518 P=0.248N P=0.500N P=0.493N P=0.252N P=0.684N | |ORDER RESTRICTED | P=0.289N (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/52 (6%) 0/54 (0%) 0/52 (0%) 0/52 (0%) 1/53 (2%) 1/51 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 3/33.26 0/38.32 0/38.60 0/36.32 1/36.61 1/41.46 1/32.33 | |POLY-3 PERCENT (g) | 9.0% 0.0% 0.0% 0.0% 2.7% 2.4% 3.1% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/25 (0%) 0/21 (0%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 222 --- --- --- 727 (T) 720 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.556 P=0.095N P=0.093N P=0.102N P=0.259N P=0.199N P=0.269N | |POLY 3 | P=0.537 P=0.094N P=0.093N P=0.102N P=0.270N P=0.231N P=0.313N | |POLY 1.5 | P=0.568 P=0.102N P=0.102N P=0.106N P=0.280N P=0.257N P=0.302N | |POLY 6 | P=0.508 P=0.083N P=0.084N P=0.100N P=0.263N P=0.206N P=0.348N | |LOGISTIC REGRESSION| P=0.606 P=0.130N P=0.171N P=0.172N P=0.322N P=0.433N P=0.309N | |COCH-ARM / FISHERS | P=0.607 P=0.115N P=0.121N P=0.121N P=0.302N P=0.316N P=0.302N | |ORDER RESTRICTED | P=0.038N* (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/54 (0%) 0/52 (0%) 0/52 (0%) 0/53 (0%) 0/51 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.36 0/38.32 0/38.60 0/36.32 0/36.61 0/41.43 2/32.53 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 6.2% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/25 (0%) 0/21 (0%) 0/16 (0%) 0/23 (0%) 1/7 (14%) | |FIRST INCIDENCE | --- --- --- --- --- --- 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** (e) (e) (e) (e) (e) P=0.172 | |POLY 3 | P=0.007 ** (e) (e) (e) (e) (e) P=0.244 | |POLY 1.5 | P=0.007 ** (e) (e) (e) (e) (e) P=0.246 | |POLY 6 | P=0.010 * (e) (e) (e) (e) (e) P=0.228 | |LOGISTIC REGRESSION| P=0.006 ** (e) (e) (e) (e) (e) P=0.243 | |COCH-ARM / FISHERS | P=0.007 ** (e) (e) (e) (e) (e) P=0.252 | |ORDER RESTRICTED | P=0.005 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/4 (0%) 2/7 (29%) 0/12 (0%) | |POLY-3 RATE (b) | 0/0.63 0/3.24 0/3.60 0/3.43 0/2.47 2/6.05 0/7.43 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 33.1% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/1 (0%) | |FIRST INCIDENCE | --- --- --- --- --- 651 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.192 (e) (e) (e) (e) P=0.367 (e) | |POLY 3 | P=0.540 (e) (e) (e) (e) P=0.710 (e) | |POLY 1.5 | P=0.555 (e) (e) (e) (e) P=0.673 (e) | |POLY 6 | P=0.481 (e) (e) (e) (e) P=0.747 (e) | |LOGISTIC REGRESSION| P=0.542 (e) (e) (e) (e) P=0.800 (e) | |COCH-ARM / FISHERS | P=0.502 (e) (e) (e) (e) P=0.583 (e) | |ORDER RESTRICTED | P=0.760 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 0/6 (0%) 0/6 (0%) 2/6 (33%) 1/4 (25%) 1/7 (14%) 0/12 (0%) | |POLY-3 RATE (b) | 0/0.63 0/3.24 0/3.60 2/4.37 1/3.38 1/6.05 0/7.43 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 45.8% 29.6% 16.5% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/1 (0%) | |FIRST INCIDENCE | --- --- --- 496 331 618 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.637 (e) (e) P=0.287 P=0.522 P=0.581 (e) | |POLY 3 | P=0.212N (e) (e) P=0.682 P=0.749 P=0.817 (e) | |POLY 1.5 | P=0.229N (e) (e) P=0.636 P=0.723 P=0.802 (e) | |POLY 6 | P=0.208N (e) (e) P=0.740 P=0.778 P=0.833 (e) | |LOGISTIC REGRESSION| P=0.410N (e) (e) P=0.581 P=0.439 P=0.851 (e) | |COCH-ARM / FISHERS | P=0.327N (e) (e) P=0.536 P=0.667 P=0.778 (e) | |ORDER RESTRICTED | P=0.764N (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 2/6 (33%) 3/6 (50%) 0/6 (0%) 0/4 (0%) 0/7 (0%) 5/12 (42%) | |POLY-3 RATE (b) | 0/0.63 2/3.86 3/4.04 0/3.43 0/2.47 0/5.66 5/9.34 | |POLY-3 PERCENT (g) | 0.0% 51.8% 74.3% 0.0% 0.0% 0.0% 53.5% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 2/2 (100%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/1 (100%) | |FIRST INCIDENCE | --- 630 602 --- --- --- 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.016 * P=0.326 P=0.573 (e) (e) (e) P=0.068 | |POLY 3 | P=0.395 P=0.673 P=0.593 (e) (e) (e) P=0.630 | |POLY 1.5 | P=0.340 P=0.618 P=0.510 (e) (e) (e) P=0.567 | |POLY 6 | P=0.467 P=0.742 P=0.784 (e) (e) (e) P=0.714 | |LOGISTIC REGRESSION| P=0.311 P=0.662 P=0.527 (e) (e) (e) P=0.494 | |COCH-ARM / FISHERS | P=0.244 P=0.536 P=0.357 (e) (e) (e) P=0.396 | |ORDER RESTRICTED | P=0.654 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 0/6 (0%) 2/6 (33%) 1/6 (17%) 1/4 (25%) 0/7 (0%) 6/12 (50%) | |POLY-3 RATE (b) | 0/0.63 0/3.24 2/4.04 1/3.97 1/2.86 0/5.66 6/10.24 | |POLY-3 PERCENT (g) | 0.0% 0.0% 49.6% 25.2% 35.0% 0.0% 58.6% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 1/2 (50%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/1 (0%) | |FIRST INCIDENCE | --- --- 602 559 618 --- 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) P=0.573 P=0.543 P=0.554 (e) P=0.018 * | |POLY 3 | P=0.066 (e) P=0.677 P=0.796 P=0.744 (e) P=0.604 | |POLY 1.5 | P=0.051 (e) P=0.629 P=0.775 P=0.715 (e) P=0.529 | |POLY 6 | P=0.089 (e) P=0.743 P=0.824 P=0.778 (e) P=0.695 | |LOGISTIC REGRESSION| P=0.027 * (e) P=0.709 P=0.783 P=0.765 (e) P=0.243 | |COCH-ARM / FISHERS | P=0.027 * (e) P=0.536 P=0.750 P=0.667 (e) P=0.308 | |ORDER RESTRICTED | P=0.637 (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/4 (0%) 0/7 (0%) 2/12 (17%) | |POLY-3 RATE (b) | 0/0.63 0/3.24 0/3.60 0/3.43 0/2.47 0/5.66 2/8.62 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 23.2% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 0/2 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/1 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.008 ** (e) (e) (e) (e) (e) P=0.281 | |POLY 3 | P=0.066 (e) (e) (e) (e) (e) P=0.782 | |POLY 1.5 | P=0.062 (e) (e) (e) (e) (e) P=0.757 | |POLY 6 | P=0.070 (e) (e) (e) (e) (e) P=0.812 | |LOGISTIC REGRESSION| P=0.027 * (e) (e) (e) (e) (e) P=0.590 | |COCH-ARM / FISHERS | P=0.047 * (e) (e) (e) (e) (e) P=0.725 | |ORDER RESTRICTED | P=0.706 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/52 (15%) 3/55 (5%) 1/53 (2%) 4/53 (8%) 5/53 (9%) 1/52 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 8/33.57 3/39.34 1/40.40 4/37.83 5/37.22 1/41.88 1/32.31 | |POLY-3 PERCENT (g) | 23.8% 7.6% 2.5% 10.6% 13.4% 2.4% 3.1% | |TERMINAL (d) | 3/15 (20%) 1/25 (4%) 0/26 (0%) 3/22 (14%) 4/16 (25%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 405 524 428 576 531 628 611 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.067N P=0.031N* P=0.005N** P=0.077N P=0.205N P=0.004N** P=0.051N | |POLY 3 | P=0.034N* P=0.052N P=0.006N** P=0.116N P=0.203N P=0.005N** P=0.015N* | |POLY 1.5 | P=0.031N* P=0.064N P=0.008N** P=0.128N P=0.223N P=0.008N** P=0.014N* | |POLY 6 | P=0.043N* P=0.038N* P=0.004N** P=0.108N P=0.190N P=0.003N** P=0.021N* | |LOGISTIC REGRESSION| P=0.030N* P=0.066N P=0.014N* P=0.117N P=0.200N P=0.011N* P=0.016N* | |COCH-ARM / FISHERS | P=0.031N* P=0.084N P=0.014N* P=0.170N P=0.265N P=0.016N* P=0.014N* | |ORDER RESTRICTED | P=0.002N** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 32/52 (62%) 33/55 (60%) 30/53 (57%) 29/53 (55%) 21/53 (40%) 23/52 (44%) 9/53 (17%) | |POLY-3 RATE (b) | 32/43.06 33/45.84 30/46.24 29/43.63 21/40.32 23/45.33 9/34.10 | |POLY-3 PERCENT (g) | 74.3% 72.0% 64.9% 66.5% 52.1% 50.7% 26.4% | |TERMINAL (d) | 11/15 (73%) 15/25 (60%) 13/26 (50%) 15/22 (68%) 7/16 (44%) 10/23 (44%) 4/7 (57%) | |FIRST INCIDENCE | 126 82 328 405 531 185 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001N** P=0.082N P=0.031N* P=0.063N P=0.016N* P=0.002N** P=0.002N** | |POLY 3 | P<0.001N** P=0.497N P=0.219N P=0.269N P=0.020N* P=0.013N* P<0.001N** | |POLY 1.5 | P<0.001N** P=0.540N P=0.295N P=0.277N P=0.022N* P=0.023N* P<0.001N** | |POLY 6 | P<0.001N** P=0.374N P=0.127N P=0.267N P=0.019N* P=0.007N** P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P=0.450N P=0.294N P=0.216N P=0.011N* P=0.045N* P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P=0.514N P=0.376N P=0.305N P=0.020N* P=0.058N P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 0/55 (0%) 0/53 (0%) 2/53 (4%) 2/53 (4%) 0/52 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 1/31.36 0/38.53 0/39.60 2/37.74 2/36.61 0/41.53 0/31.91 | |POLY-3 PERCENT (g) | 3.2% 0.0% 0.0% 5.3% 5.5% 0.0% 0.0% | |TERMINAL (d) | 1/15 (7%) 0/25 (0%) 0/26 (0%) 1/22 (5%) 2/16 (13%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 727 (T) --- --- 607 727 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.446N P=0.398N P=0.390N P=0.607 P=0.523 P=0.415N P=0.652N | |POLY 3 | P=0.305N P=0.459N P=0.454N P=0.564 P=0.554 P=0.445N P=0.497N | |POLY 1.5 | P=0.304N P=0.472N P=0.469N P=0.547 P=0.536 P=0.464N P=0.493N | |POLY 6 | P=0.341N P=0.439N P=0.435N P=0.583 P=0.571 P=0.424N P=0.512N | |LOGISTIC REGRESSION| P=0.349N (e) (e) P=0.572 P=0.523 (e) (e) | |COCH-ARM / FISHERS | P=0.314N P=0.486N P=0.495N P=0.507 P=0.507 P=0.500N P=0.495N | |ORDER RESTRICTED | P=0.369N (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 2/55 (4%) 0/53 (0%) 1/53 (2%) 0/53 (0%) 0/52 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 2/31.43 2/39.32 0/39.60 1/37.83 0/36.61 0/41.53 0/31.91 | |POLY-3 PERCENT (g) | 6.4% 5.1% 0.0% 2.6% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/15 (7%) 1/25 (4%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 709 434 --- 576 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.083N P=0.535N P=0.129N P=0.395N P=0.203N P=0.137N P=0.410N | |POLY 3 | P=0.065N P=0.611N P=0.189N P=0.435N P=0.204N P=0.181N P=0.232N | |POLY 1.5 | P=0.069N P=0.640N P=0.204N P=0.453N P=0.214N P=0.199N P=0.229N | |POLY 6 | P=0.067N P=0.570N P=0.172N P=0.418N P=0.194N P=0.163N P=0.249N | |LOGISTIC REGRESSION| P=0.071N P=0.643N P=0.141N P=0.439N P=0.186N P=0.130N P=0.330N | |COCH-ARM / FISHERS | P=0.073N P=0.670N P=0.243N P=0.493N P=0.243N P=0.248N P=0.243N | |ORDER RESTRICTED | P=0.071N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mesentery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/1 (100%) 0/0 (0%) 0/4 (0%) 0/2 (0%) 0/7 (0%) 0/13 (0%) 3/11 (27%) | |POLY-3 RATE (b) | 1/1.00 0/0.00 0/3.52 0/2.00 0/6.22 0/10.00 3/8.85 | |POLY-3 PERCENT (g) | 100.0% 0.0% 0.0% 0.0% 0.0% 0.0% 33.9% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/3 (0%) 0/2 (0%) 0/4 (0%) 0/3 (0%) 1/2 (50%) | |FIRST INCIDENCE | 391 --- --- --- --- --- 562 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.011 * (e) P=0.468N P=0.468N P=0.473N P=0.440N P=0.544 | |POLY 3 | (e) (e) P<0.001N** P=0.333 P<0.001N** P<0.001N** P=0.408N | |POLY 1.5 | (e) (e) P<0.001N** P=0.333 P<0.001N** P<0.001N** P=0.379N | |POLY 6 | (e) (e) P<0.001N** P=0.333 P<0.001N** P<0.001N** P=0.472N | |LOGISTIC REGRESSION| P=0.170 (e) (e) (e) (e) P=0.168N P=0.983N | |COCH-ARM / FISHERS | P=0.181 (e) P=0.200N P=0.333N P=0.125N P=0.071N P=0.333N | |ORDER RESTRICTED | (e) (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mesentery: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/1 (0%) 0/0 (0%) 2/4 (50%) 2/2 (100%) 6/7 (86%) 10/13 (77%) 7/11 (64%) | |POLY-3 RATE (b) | 0/0.16 0/0.00 2/3.52 2/2.00 6/6.85 10/11.50 7/9.70 | |POLY-3 PERCENT (g) | 0.0% 0.0% 56.8% 100.0% 87.6% 87.0% 72.2% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 2/3 (67%) 2/2 (100%) 4/4 (100%) 3/3 (100%) 1/2 (50%) | |FIRST INCIDENCE | --- --- 727 (T) 727 (T) 618 573 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) P=1.000 P=1.000 P=0.310 P=0.050 P=0.014 * | |POLY 3 | (e) (e) P=0.800 P=0.333 P=0.873 P=0.899 P=0.840 | |POLY 1.5 | (e) (e) P=0.731 P=0.333 P=0.699 P=0.708 P=0.711 | |POLY 6 | (e) (e) P=0.843 P=0.333 P=0.955 P=0.983 P=0.922 | |LOGISTIC REGRESSION| P=0.537 (e) P=1.000 P=1.000 (e) P=0.978 P=0.991 | |COCH-ARM / FISHERS | P=0.567N (e) P=0.600 P=0.333 P=0.250 P=0.286 P=0.417 | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Nose: Respiratory Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/54 (0%) 1/52 (2%) 1/53 (2%) 2/52 (4%) 2/53 (4%) 1/53 (2%) | |POLY-3 RATE (b) | 2/32.23 0/37.53 1/39.58 1/37.32 2/36.06 2/42.16 1/32.29 | |POLY-3 PERCENT (g) | 6.2% 0.0% 2.5% 2.7% 5.6% 4.7% 3.1% | |TERMINAL (d) | 1/15 (7%) 0/24 (0%) 0/26 (0%) 1/22 (5%) 1/16 (6%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | 391 --- 709 727 (T) 607 720 618 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.323 P=0.185N P=0.365N P=0.395N P=0.648N P=0.550N P=0.577N | |POLY 3 | P=0.432 P=0.204N P=0.429N P=0.449N P=0.654N P=0.593N P=0.499N | |POLY 1.5 | P=0.470 P=0.216N P=0.455N P=0.461N P=0.671N P=0.628N P=0.493N | |POLY 6 | P=0.376 P=0.186N P=0.398N P=0.437N P=0.639N P=0.555N P=0.526N | |LOGISTIC REGRESSION| P=0.497 P=0.240N P=0.501N P=0.484N P=0.689N P=0.658N P=0.499N | |COCH-ARM / FISHERS | P=0.508 P=0.243N P=0.507N P=0.500N P=0.684 P=0.691N P=0.500N | |ORDER RESTRICTED | P=0.495N (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Nose: Turbinate | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/54 (0%) 1/52 (2%) 1/53 (2%) 2/52 (4%) 0/53 (0%) 4/53 (8%) | |POLY-3 RATE (b) | 2/31.81 0/37.53 1/39.51 1/37.32 2/36.29 0/42.13 4/32.97 | |POLY-3 PERCENT (g) | 6.3% 0.0% 2.5% 2.7% 5.5% 0.0% 12.1% | |TERMINAL (d) | 1/15 (7%) 0/24 (0%) 1/26 (4%) 1/22 (5%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 603 --- 727 (T) 727 (T) 607 --- 611 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.020 * P=0.165N P=0.344N P=0.393N P=0.608N P=0.155N P=0.251 | |POLY 3 | P=0.067 P=0.201N P=0.425N P=0.444N P=0.647N P=0.181N P=0.350 | |POLY 1.5 | P=0.067 P=0.214N P=0.452N P=0.458N P=0.666N P=0.198N P=0.354 | |POLY 6 | P=0.070 P=0.184N P=0.396N P=0.433N P=0.629N P=0.164N P=0.323 | |LOGISTIC REGRESSION| P=0.053 P=0.201N P=0.405N P=0.429N P=0.665N P=0.184N P=0.333 | |COCH-ARM / FISHERS | P=0.065 P=0.243N P=0.507N P=0.500N P=0.684 P=0.248N P=0.339 | |ORDER RESTRICTED | P=0.049 * (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Oral Mucosa: Gingival | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/1 (100%) 0/1 (0%) 2/3 (67%) 2/4 (50%) 0/2 (0%) 4/6 (67%) 3/11 (27%) | |POLY-3 RATE (b) | 1/1.00 0/0.82 2/2.72 2/4.00 0/1.61 4/5.29 3/8.09 | |POLY-3 PERCENT (g) | 100.0% 0.0% 73.6% 50.0% 0.0% 75.6% 37.1% | |TERMINAL (d) | 1/1 (100%) 0/0 (0%) 0/0 (0%) 1/3 (33%) 0/1 (0%) 3/3 (100%) 1/1 (100%) | |FIRST INCIDENCE | 727 (T) --- 688 658 --- 651 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.034 * P=1.000 P=0.369 P=0.735N P=0.500N P=0.598 P=0.247 | |POLY 3 | P=0.313N P=1.000 P=0.786N P=0.577N P=0.085N P=0.783N P=0.438N | |POLY 1.5 | P=0.251N P=1.000 P=0.737N P=0.577N P<0.001N** P=0.741N P=0.392N | |POLY 6 | P=0.436N P=1.000 P=0.885N P=0.577N P=0.303N P=0.822N P=0.546N | |LOGISTIC REGRESSION| P=0.478N (e) (e) (e) (e) P=0.872N P=0.529N | |COCH-ARM / FISHERS | P=0.197N P=0.500N P=0.750N P=0.600N P=0.333N P=0.714N P=0.333N | |ORDER RESTRICTED | P=0.448N (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Ovary | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 45/52 (87%) 49/54 (91%) 46/53 (87%) 45/52 (87%) 47/52 (90%) 46/52 (88%) 33/53 (62%) | |POLY-3 RATE (b) | 45/46.65 49/52.02 46/50.50 45/49.66 47/49.76 46/50.55 33/43.43 | |POLY-3 PERCENT (g) | 96.5% 94.2% 91.1% 90.6% 94.5% 91.0% 76.0% | |TERMINAL (d) | 14/15 (93%) 22/25 (88%) 23/26 (89%) 19/22 (86%) 15/16 (94%) 22/23 (96%) 5/7 (71%) | |FIRST INCIDENCE | 126 223 188 124 163 320 243 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.383 P=0.075N P=0.020N* P=0.090N P=0.310N P=0.016N* P=0.336N | |POLY 3 | P<0.001N** P=0.477N P=0.234N P=0.204N P=0.508N P=0.232N P<0.001N** | |POLY 1.5 | P<0.001N** P=0.654N P=0.314N P=0.271N P=0.619N P=0.360N P<0.001N** | |POLY 6 | P=0.005N** P=0.376N P=0.217N P=0.218N P=0.539N P=0.195N P=0.005N** | |LOGISTIC REGRESSION| P<0.001N** P=0.447 P=0.394N P=0.388N P=0.492 P=0.388N P=0.002N** | |COCH-ARM / FISHERS | P<0.001N** P=0.354 P=0.598 P=0.613N P=0.380 P=0.500 P=0.004N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/52 (23%) 17/54 (31%) 17/53 (32%) 15/52 (29%) 16/52 (31%) 18/52 (35%) 11/53 (21%) | |POLY-3 RATE (b) | 12/33.36 17/41.28 17/40.57 15/38.87 16/40.40 18/44.23 11/35.26 | |POLY-3 PERCENT (g) | 36.0% 41.2% 41.9% 38.6% 39.6% 40.7% 31.2% | |TERMINAL (d) | 7/15 (47%) 10/25 (40%) 15/26 (58%) 10/22 (46%) 6/16 (38%) 9/23 (39%) 1/7 (14%) | |FIRST INCIDENCE | 547 356 541 496 331 498 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.164 P=0.505N P=0.411N P=0.481N P=0.419 P=0.552N P=0.380 | |POLY 3 | P=0.263N P=0.411 P=0.387 P=0.506 P=0.468 P=0.425 P=0.433N | |POLY 1.5 | P=0.251N P=0.321 P=0.318 P=0.453 P=0.378 P=0.304 P=0.440N | |POLY 6 | P=0.317N P=0.545 P=0.469 P=0.553 P=0.567 P=0.569 P=0.465N | |LOGISTIC REGRESSION| P=0.310N P=0.379 P=0.549 P=0.547 P=0.348 P=0.415 P=0.492N | |COCH-ARM / FISHERS | P=0.261N P=0.226 P=0.208 P=0.328 P=0.254 P=0.140 P=0.479N | |ORDER RESTRICTED | P=0.449N (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Ovary | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 1/54 (2%) 0/53 (0%) 0/52 (0%) 0/52 (0%) 2/52 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.36 1/38.90 0/39.60 0/36.94 0/35.84 2/41.53 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 2.6% 0.0% 0.0% 0.0% 4.8% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 2/23 (9%) 0/7 (0%) | |FIRST INCIDENCE | --- 546 --- --- --- 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.407 P=0.526 (e) (e) (e) P=0.336 (e) | |POLY 3 | P=0.389 P=0.543 (e) (e) (e) P=0.304 (e) | |POLY 1.5 | P=0.445 P=0.527 (e) (e) (e) P=0.280 (e) | |POLY 6 | P=0.323 P=0.565 (e) (e) (e) P=0.333 (e) | |LOGISTIC REGRESSION| P=0.503 P=0.497 (e) (e) (e) P=0.336 (e) | |COCH-ARM / FISHERS | P=0.513 P=0.509 (e) (e) (e) P=0.248 (e) | |ORDER RESTRICTED | P=0.322 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Oviduct | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/1 (100%) 1/1 (100%) 0/0 (0%) 0/0 (0%) 0/1 (0%) 2/3 (67%) 1/1 (100%) | |POLY-3 RATE (b) | 1/1.00 1/1.00 0/0.00 0/0.00 0/0.98 2/2.72 1/1.00 | |POLY-3 PERCENT (g) | 100.0% 100.0% 0.0% 0.0% 0.0% 73.6% 100.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/2 (100%) 1/1 (100%) | |FIRST INCIDENCE | 709 546 --- --- --- 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.253N (e) (e) (e) P=0.477N P=0.411N (e) | |POLY 3 | (e) (e) (e) (e) P=1.000 P=0.786N (e) | |POLY 1.5 | (e) (e) (e) (e) P=1.000 P=0.737N (e) | |POLY 6 | (e) (e) (e) (e) P=1.000 P=0.885N (e) | |LOGISTIC REGRESSION| P=0.748N (e) (e) (e) (e) P=0.411N (e) | |COCH-ARM / FISHERS | P=0.719 (e) (e) (e) P=0.500N P=0.750N (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/51 (10%) 1/55 (2%) 3/53 (6%) 4/53 (8%) 4/53 (8%) 6/52 (12%) 13/51 (25%) | |POLY-3 RATE (b) | 5/32.80 1/38.53 3/40.81 4/38.15 4/37.40 6/43.08 13/35.71 | |POLY-3 PERCENT (g) | 15.2% 2.6% 7.4% 10.5% 10.7% 13.9% 36.4% | |TERMINAL (d) | 3/15 (20%) 1/25 (4%) 1/26 (4%) 3/22 (14%) 0/16 (0%) 1/23 (4%) 2/7 (29%) | |FIRST INCIDENCE | 391 727 (T) 300 405 618 573 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.041N* P=0.182N P=0.315N P=0.405N P=0.478N P=0.019 * | |POLY 3 | P<0.001 ** P=0.066N P=0.242N P=0.404N P=0.416N P=0.566N P=0.037 * | |POLY 1.5 | P<0.001 ** P=0.075N P=0.275N P=0.424N P=0.442N P=0.623 P=0.034 * | |POLY 6 | P<0.001 ** P=0.053N P=0.203N P=0.385N P=0.387N P=0.486N P=0.040 * | |LOGISTIC REGRESSION| P<0.001 ** P=0.075N P=0.347N P=0.439N P=0.435N P=0.563 P=0.034 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.086N P=0.336N P=0.475N P=0.475N P=0.514 P=0.034 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/51 (10%) 3/55 (5%) 2/53 (4%) 7/53 (13%) 2/53 (4%) 11/52 (21%) 18/51 (35%) | |POLY-3 RATE (b) | 5/31.43 3/38.53 2/40.53 7/38.15 2/37.14 11/43.58 18/37.39 | |POLY-3 PERCENT (g) | 15.9% 7.8% 4.9% 18.4% 5.4% 25.2% 48.1% | |TERMINAL (d) | 4/15 (27%) 3/25 (12%) 1/26 (4%) 6/22 (27%) 0/16 (0%) 2/23 (9%) 2/7 (29%) | |FIRST INCIDENCE | 705 727 (T) 300 405 618 573 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.120N P=0.072N P=0.612N P=0.164N P=0.382 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.247N P=0.124N P=0.520 P=0.149N P=0.248 P=0.003 ** | |POLY 1.5 | P<0.001 ** P=0.280N P=0.151N P=0.484 P=0.170N P=0.175 P=0.002 ** | |POLY 6 | P<0.001 ** P=0.201N P=0.097N P=0.558 P=0.128N P=0.359 P=0.005 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.109N P=0.145N P=0.546 P=0.132N P=0.244 P=0.002 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.316N P=0.203N P=0.408 P=0.203N P=0.093 P=0.002 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/55 (0%) 1/53 (2%) 4/53 (8%) 9/53 (17%) 20/52 (38%) 23/51 (45%) | |POLY-3 RATE (b) | 0/31.35 0/38.53 1/39.60 4/39.05 9/37.20 20/42.74 23/36.28 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.5% 10.2% 24.2% 46.8% 63.4% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/26 (4%) 0/22 (0%) 6/16 (38%) 14/23 (61%) 6/7 (86%) | |FIRST INCIDENCE | --- --- 727 (T) 595 607 618 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) P=0.610 P=0.092 P=0.004 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) P=0.546 P=0.092 P=0.003 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) P=0.531 P=0.082 P=0.003 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) P=0.565 P=0.106 P=0.004 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) P=0.610 P=0.065 P=0.005 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.510 P=0.064 P=0.002 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 4/55 (7%) 2/53 (4%) 4/53 (8%) 8/53 (15%) 15/52 (29%) 11/51 (22%) | |POLY-3 RATE (b) | 0/31.35 4/39.52 2/39.60 4/38.50 8/37.31 15/42.61 11/35.04 | |POLY-3 PERCENT (g) | 0.0% 10.1% 5.1% 10.4% 21.4% 35.2% 31.4% | |TERMINAL (d) | 0/15 (0%) 2/25 (8%) 2/26 (8%) 2/22 (9%) 5/16 (31%) 8/23 (35%) 2/7 (29%) | |FIRST INCIDENCE | --- 253 727 (T) 448 618 588 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.132 P=0.365 P=0.106 P=0.009 ** P=0.002 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.094 P=0.292 P=0.089 P=0.007 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.082 P=0.273 P=0.081 P=0.006 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.114 P=0.316 P=0.099 P=0.008 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.074 P=0.365 P=0.073 P=0.010 * P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.069 P=0.257 P=0.064 P=0.003 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas: Duct | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/55 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 0/52 (0%) 2/51 (4%) | |POLY-3 RATE (b) | 0/31.35 0/38.53 0/39.60 0/37.32 0/36.61 0/41.53 2/31.51 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 6.4% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- 603 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** (e) (e) (e) (e) (e) P=0.230 | |POLY 3 | P=0.006 ** (e) (e) (e) (e) (e) P=0.236 | |POLY 1.5 | P=0.006 ** (e) (e) (e) (e) (e) P=0.239 | |POLY 6 | P=0.008 ** (e) (e) (e) (e) (e) P=0.225 | |LOGISTIC REGRESSION| P=0.005 ** (e) (e) (e) (e) (e) P=0.233 | |COCH-ARM / FISHERS | P=0.006 ** (e) (e) (e) (e) (e) P=0.248 | |ORDER RESTRICTED | P=0.005 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas: Duct | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/55 (0%) 0/53 (0%) 0/53 (0%) 0/53 (0%) 2/52 (4%) 0/51 (0%) | |POLY-3 RATE (b) | 0/31.35 0/38.53 0/39.60 0/37.32 0/36.61 2/41.71 0/30.95 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 4.8% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- --- 678 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.178 (e) (e) (e) (e) P=0.362 (e) | |POLY 3 | P=0.159 (e) (e) (e) (e) P=0.305 (e) | |POLY 1.5 | P=0.208 (e) (e) (e) (e) P=0.281 (e) | |POLY 6 | P=0.108 (e) (e) (e) (e) P=0.335 (e) | |LOGISTIC REGRESSION| P=0.236 (e) (e) (e) (e) P=0.329 (e) | |COCH-ARM / FISHERS | P=0.282 (e) (e) (e) (e) P=0.252 (e) | |ORDER RESTRICTED | P=0.228 (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Parathyroid Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/47 (0%) 1/50 (2%) 1/48 (2%) 2/46 (4%) 1/49 (2%) 1/47 (2%) 0/46 (0%) | |POLY-3 RATE (b) | 0/27.62 1/35.62 1/37.40 2/34.68 1/33.12 1/38.40 0/28.20 | |POLY-3 PERCENT (g) | 0.0% 2.8% 2.7% 5.8% 3.0% 2.6% 0.0% | |TERMINAL (d) | 0/13 (0%) 1/24 (4%) 0/24 (0%) 0/21 (0%) 1/15 (7%) 0/20 (0%) 0/5 (0%) | |FIRST INCIDENCE | --- 727 (T) 376 559 727 (T) 573 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.425N P=0.622 P=0.521 P=0.283 P=0.529 P=0.566 (e) | |POLY 3 | P=0.353N P=0.550 P=0.559 P=0.291 P=0.536 P=0.564 (e) | |POLY 1.5 | P=0.351N P=0.535 P=0.541 P=0.271 P=0.527 P=0.543 (e) | |POLY 6 | P=0.396N P=0.571 P=0.580 P=0.313 P=0.545 P=0.586 (e) | |LOGISTIC REGRESSION| P=0.374N P=0.622 P=0.376 P=0.217 P=0.529 P=0.469 (e) | |COCH-ARM / FISHERS | P=0.371N P=0.515 P=0.505 P=0.242 P=0.510 P=0.500 (e) | |ORDER RESTRICTED | P=0.493 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pituitary Gland | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 14/51 (27%) 15/54 (28%) 22/53 (42%) 12/53 (23%) 16/53 (30%) 19/53 (36%) 9/53 (17%) | |POLY-3 RATE (b) | 14/33.32 15/40.05 22/44.01 12/38.05 16/38.31 19/44.06 9/33.36 | |POLY-3 PERCENT (g) | 42.0% 37.5% 50.0% 31.5% 41.8% 43.1% 27.0% | |TERMINAL (d) | 7/15 (47%) 7/25 (28%) 13/26 (50%) 10/22 (46%) 8/16 (50%) 12/23 (52%) 3/7 (43%) | |FIRST INCIDENCE | 546 434 328 487 607 588 588 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.299 P=0.194N P=0.572 P=0.108N P=0.557N P=0.410N P=0.573N | |POLY 3 | P=0.139N P=0.436N P=0.317 P=0.243N P=0.590N P=0.554 P=0.139N | |POLY 1.5 | P=0.105N P=0.507N P=0.223 P=0.262N P=0.561 P=0.444 P=0.127N | |POLY 6 | P=0.251N P=0.337N P=0.433 P=0.252N P=0.569N P=0.531N P=0.202N | |LOGISTIC REGRESSION| P=0.126N P=0.422N P=0.225 P=0.176N P=0.500N P=0.536N P=0.176N | |COCH-ARM / FISHERS | P=0.094N P=0.572 P=0.097 P=0.367N P=0.464 P=0.239 P=0.147N | |ORDER RESTRICTED | P=0.164N (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pituitary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 3/54 (6%) 1/53 (2%) 1/53 (2%) 0/53 (0%) 2/53 (4%) 1/53 (2%) | |POLY-3 RATE (b) | 0/30.88 3/38.75 1/39.60 1/37.76 0/36.61 2/42.60 1/32.52 | |POLY-3 PERCENT (g) | 0.0% 7.7% 2.5% 2.7% 0.0% 4.7% 3.1% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 1/26 (4%) 0/22 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | --- 448 727 (T) 600 --- 588 530 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.504 P=0.187 P=0.610 P=0.531 (e) P=0.329 P=0.525 | |POLY 3 | P=0.571 P=0.163 P=0.549 P=0.540 (e) P=0.314 P=0.510 | |POLY 1.5 | P=0.584N P=0.148 P=0.535 P=0.531 (e) P=0.290 P=0.513 | |POLY 6 | P=0.553 P=0.189 P=0.566 P=0.549 (e) P=0.342 P=0.496 | |LOGISTIC REGRESSION| P=0.595N P=0.134 P=0.610 P=0.508 (e) P=0.278 P=0.503 | |COCH-ARM / FISHERS | P=0.594N P=0.132 P=0.510 P=0.510 (e) P=0.257 P=0.510 | |ORDER RESTRICTED | P=0.370 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pituitary Gland | | Cytoplasmic Alteration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 1/54 (2%) 1/53 (2%) 1/53 (2%) 3/53 (6%) 1/53 (2%) 0/53 (0%) | |POLY-3 RATE (b) | 0/30.88 1/37.71 1/39.60 1/37.32 3/36.91 1/42.13 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 2.7% 2.5% 2.7% 8.1% 2.4% 0.0% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 1/26 (4%) 1/22 (5%) 2/16 (13%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | --- 727 (T) 727 (T) 727 (T) 645 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.596 P=0.602 P=0.610 P=0.576 P=0.145 P=0.585 (e) | |POLY 3 | P=0.419N P=0.540 P=0.549 P=0.538 P=0.152 P=0.561 (e) | |POLY 1.5 | P=0.411N P=0.527 P=0.535 P=0.530 P=0.142 P=0.543 (e) | |POLY 6 | P=0.469N P=0.558 P=0.566 P=0.545 P=0.161 P=0.579 (e) | |LOGISTIC REGRESSION| P=0.534N P=0.602 P=0.610 P=0.576 P=0.159 P=0.585 (e) | |COCH-ARM / FISHERS | P=0.417N P=0.514 P=0.510 P=0.510 P=0.129 P=0.510 (e) | |ORDER RESTRICTED | P=0.390 (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG 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%) 21/53 (40%) 26/53 (49%) 17/53 (32%) | |POLY-3 RATE (b) | 18/36.64 20/40.01 23/42.91 17/41.61 21/40.94 26/43.52 17/36.71 | |POLY-3 PERCENT (g) | 49.1% 50.0% 53.6% 40.9% 51.3% 59.7% 46.3% | |TERMINAL (d) | 4/15 (27%) 13/25 (52%) 15/26 (58%) 8/22 (36%) 7/16 (44%) 18/23 (78%) 3/7 (43%) | |FIRST INCIDENCE | 400 546 498 436 541 637 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.029 * P=0.215N P=0.328N P=0.208N P=0.532N P=0.469N P=0.396 | |POLY 3 | P=0.444 P=0.562 P=0.429 P=0.301N P=0.515 P=0.224 P=0.497N | |POLY 1.5 | P=0.524 P=0.545 P=0.382 P=0.317N P=0.483 P=0.200 P=0.445N | |POLY 6 | P=0.286 P=0.593 P=0.465 P=0.318N P=0.531 P=0.219 P=0.582 | |LOGISTIC REGRESSION| P=0.515 P=0.501N P=0.475 P=0.326N P=0.538 P=0.434 P=0.425N | |COCH-ARM / FISHERS | P=0.481N P=0.507 P=0.260 P=0.444N P=0.400 P=0.111 P=0.444N | |ORDER RESTRICTED | P=0.614 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 39/52 (75%) 43/55 (78%) 46/52 (88%) 45/53 (85%) 41/53 (77%) 42/52 (81%) 37/52 (71%) | |POLY-3 RATE (b) | 39/47.51 43/47.53 46/48.28 45/49.58 41/47.65 42/47.95 37/44.38 | |POLY-3 PERCENT (g) | 82.1% 90.5% 95.3% 90.8% 86.1% 87.6% 83.4% | |TERMINAL (d) | 8/15 (53%) 23/25 (92%) 24/25 (96%) 21/22 (96%) 15/16 (94%) 22/23 (96%) 6/7 (86%) | |FIRST INCIDENCE | 126 223 188 385 40 320 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.062 P=0.112N P=0.174N P=0.336N P=0.353N P=0.056N P=0.344 | |POLY 3 | P=0.177N P=0.170 P=0.033 * P=0.155 P=0.395 P=0.313 P=0.550 | |POLY 1.5 | P=0.111N P=0.251 P=0.039 * P=0.168 P=0.472 P=0.337 P=0.534N | |POLY 6 | P=0.391N P=0.114 P=0.032 * P=0.119 P=0.258 P=0.260 P=0.327 | |LOGISTIC REGRESSION| P=0.115N P=0.522 P=0.115 P=0.202 P=0.514 P=0.491 P=0.404N | |COCH-ARM / FISHERS | P=0.118N P=0.436 P=0.063 P=0.153 P=0.478 P=0.319 P=0.413N | |ORDER RESTRICTED | P=0.236 (e) (e) (e) (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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Spleen | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/55 (0%) 1/52 (2%) 0/53 (0%) 1/53 (2%) 1/52 (2%) 3/52 (6%) | |POLY-3 RATE (b) | 0/31.36 0/38.53 1/38.98 0/37.32 1/36.86 1/41.53 3/32.34 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.6% 0.0% 2.7% 2.4% 9.3% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/25 (0%) 0/22 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 621 --- 659 727 (T) 603 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004 ** (e) P=0.584 (e) P=0.548 P=0.585 P=0.146 | |POLY 3 | P=0.009 ** (e) P=0.543 (e) P=0.532 P=0.555 P=0.121 | |POLY 1.5 | P=0.009 ** (e) P=0.527 (e) P=0.521 P=0.536 P=0.123 | |POLY 6 | P=0.009 ** (e) P=0.563 (e) P=0.543 P=0.576 P=0.112 | |LOGISTIC REGRESSION| P=0.008 ** (e) P=0.509 (e) P=0.526 P=0.585 P=0.121 | |COCH-ARM / FISHERS | P=0.009 ** (e) P=0.500 (e) P=0.505 P=0.500 P=0.121 | |ORDER RESTRICTED | P=0.014 * (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 49/52 (94%) 50/55 (91%) 51/52 (98%) 51/53 (96%) 52/53 (98%) 52/52 (100%) 50/52 (96%) | |POLY-3 RATE (b) | 49/49.42 50/52.81 51/51.32 51/52.28 52/52.75 52/52.00 50/50.58 | |POLY-3 PERCENT (g) | 99.2% 94.7% 99.4% 97.6% 98.6% 100.0% 98.9% | |TERMINAL (d) | 15/15 (100%) 24/25 (96%) 25/25 (100%) 22/22 (100%) 16/16 (100%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | 126 202 188 124 40 185 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004 ** P=0.030N* P=0.026N* P=0.114N P=0.338N P=0.023N* P=0.149 | |POLY 3 | P=0.224 P=0.209N P=0.972 P=0.575N P=0.807N P=0.958 P=0.895N | |POLY 1.5 | P=0.179 P=0.266N P=0.743 P=0.634N P=0.779 P=0.503 P=0.787 | |POLY 6 | P=0.239 P=0.189N P=1.000 P=0.678N P=0.845N P=1.000 P=0.985N | |LOGISTIC REGRESSION| P=0.179 P=0.320N P=0.493 P=0.672 P=0.347 P=0.303 P=0.541 | |COCH-ARM / FISHERS | P=0.172 P=0.390N P=0.309 P=0.491 P=0.302 P=0.121 P=0.500 | |ORDER RESTRICTED | P=0.223 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 53 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 5/55 (9%) 3/52 (6%) 2/53 (4%) 5/53 (9%) 3/52 (6%) 6/52 (12%) | |POLY-3 RATE (b) | 0/31.36 5/42.56 3/40.37 2/38.51 5/39.29 3/42.88 6/33.93 | |POLY-3 PERCENT (g) | 0.0% 11.8% 7.4% 5.2% 12.7% 7.0% 17.7% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/25 (4%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 202 328 500 163 440 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.058 P=0.049 * P=0.167 P=0.272 P=0.056 P=0.210 P=0.028 * | |POLY 3 | P=0.071 P=0.065 P=0.170 P=0.285 P=0.053 P=0.185 P=0.018 * | |POLY 1.5 | P=0.068 P=0.052 P=0.150 P=0.271 P=0.045 * P=0.159 P=0.017 * | |POLY 6 | P=0.072 P=0.088 P=0.195 P=0.300 P=0.064 P=0.218 P=0.016 * | |LOGISTIC REGRESSION| P=0.065 P=0.022 * P=0.070 P=0.202 P=0.026 * P=0.088 P=0.018 * | |COCH-ARM / FISHERS | P=0.063 P=0.033 * P=0.121 P=0.252 P=0.030 * P=0.121 P=0.013 * | |ORDER RESTRICTED | P=0.013 * (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Spleen: Red Pulp | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/55 (0%) 4/52 (8%) 1/53 (2%) 1/53 (2%) 0/52 (0%) 2/52 (4%) | |POLY-3 RATE (b) | 0/31.36 0/38.53 4/40.50 1/38.00 1/36.99 0/41.53 2/32.44 | |POLY-3 PERCENT (g) | 0.0% 0.0% 9.9% 2.6% 2.7% 0.0% 6.2% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/25 (4%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 328 500 618 --- 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.378 (e) P=0.113 P=0.524 P=0.559 (e) P=0.260 | |POLY 3 | P=0.467 (e) P=0.099 P=0.538 P=0.533 (e) P=0.243 | |POLY 1.5 | P=0.452 (e) P=0.083 P=0.528 P=0.522 (e) P=0.244 | |POLY 6 | P=0.489 (e) P=0.122 P=0.549 P=0.544 (e) P=0.230 | |LOGISTIC REGRESSION| P=0.413 (e) P=0.042 * P=0.453 P=0.511 (e) P=0.227 | |COCH-ARM / FISHERS | P=0.411 (e) P=0.059 P=0.505 P=0.505 (e) P=0.248 | |ORDER RESTRICTED | P=0.162 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 54 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 3/55 (5%) 1/53 (2%) 1/53 (2%) 3/53 (6%) 1/51 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.36 3/38.71 1/39.75 1/37.58 3/37.14 1/41.62 2/32.22 | |POLY-3 PERCENT (g) | 0.0% 7.8% 2.5% 2.7% 8.1% 2.4% 6.2% | |TERMINAL (d) | 0/15 (0%) 2/25 (8%) 0/26 (0%) 0/22 (0%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 681 688 658 618 678 681 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.248 P=0.226 P=0.595 P=0.568 P=0.162 P=0.627 P=0.192 | |POLY 3 | P=0.420 P=0.159 P=0.547 P=0.536 P=0.150 P=0.555 P=0.241 | |POLY 1.5 | P=0.423 P=0.145 P=0.531 P=0.527 P=0.139 P=0.535 P=0.245 | |POLY 6 | P=0.424 P=0.184 P=0.566 P=0.546 P=0.163 P=0.577 P=0.226 | |LOGISTIC REGRESSION| P=0.370 P=0.193 P=0.557 P=0.530 P=0.150 P=0.553 P=0.207 | |COCH-ARM / FISHERS | P=0.418 P=0.132 P=0.505 P=0.505 P=0.125 P=0.495 P=0.252 | |ORDER RESTRICTED | P=0.231 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/52 (6%) 4/55 (7%) 6/53 (11%) 2/53 (4%) 5/53 (9%) 6/51 (12%) 8/53 (15%) | |POLY-3 RATE (b) | 3/32.29 4/38.74 6/41.70 2/38.13 5/38.68 6/42.62 8/34.42 | |POLY-3 PERCENT (g) | 9.3% 10.3% 14.4% 5.3% 12.9% 14.1% 23.2% | |TERMINAL (d) | 1/15 (7%) 2/25 (8%) 2/26 (8%) 0/22 (0%) 1/16 (6%) 2/23 (9%) 1/7 (14%) | |FIRST INCIDENCE | 391 681 328 559 301 320 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.005 ** P=0.567N P=0.446 P=0.377N P=0.440 P=0.484 P=0.046 * | |POLY 3 | P=0.037 * P=0.600 P=0.381 P=0.424N P=0.458 P=0.395 P=0.109 | |POLY 1.5 | P=0.040 * P=0.567 P=0.331 P=0.444N P=0.423 P=0.336 P=0.113 | |POLY 6 | P=0.030 * P=0.649 P=0.446 P=0.403N P=0.496 P=0.462 P=0.093 | |LOGISTIC REGRESSION| P=0.038 * P=0.605 P=0.246 P=0.483N P=0.362 P=0.257 P=0.109 | |COCH-ARM / FISHERS | P=0.039 * P=0.532 P=0.254 P=0.491N P=0.369 P=0.234 P=0.107 | |ORDER RESTRICTED | P=0.088 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 55 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 1/55 (2%) 2/53 (4%) 1/53 (2%) 1/53 (2%) 0/51 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.36 1/38.56 2/40.19 1/37.58 1/36.61 0/41.43 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 2.6% 5.0% 2.7% 2.7% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 720 602 658 727 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.253N P=0.624 P=0.328 P=0.568 P=0.513 (e) (e) | |POLY 3 | P=0.165N P=0.541 P=0.296 P=0.536 P=0.531 (e) (e) | |POLY 1.5 | P=0.179N P=0.528 P=0.275 P=0.527 P=0.521 (e) (e) | |POLY 6 | P=0.168N P=0.561 P=0.324 P=0.546 P=0.540 (e) (e) | |LOGISTIC REGRESSION| P=0.210N P=0.596 P=0.263 P=0.530 P=0.513 (e) (e) | |COCH-ARM / FISHERS | P=0.208N P=0.514 P=0.252 P=0.505 P=0.505 (e) (e) | |ORDER RESTRICTED | P=0.441N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 0/55 (0%) 1/53 (2%) 1/53 (2%) 0/53 (0%) 1/51 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 1/32.34 0/38.53 1/40.46 1/37.32 0/36.61 1/41.94 2/33.34 | |POLY-3 PERCENT (g) | 3.1% 0.0% 2.5% 2.7% 0.0% 2.4% 6.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 1/22 (5%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 201 --- 376 727 (T) --- 573 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.151 P=0.485N P=0.744N P=0.714N P=0.496N P=0.719N P=0.524 | |POLY 3 | P=0.160 P=0.465N P=0.709N P=0.729N P=0.475N P=0.699N P=0.511 | |POLY 1.5 | P=0.169 P=0.477N P=0.727N P=0.737N P=0.484N P=0.724N P=0.515 | |POLY 6 | P=0.156 P=0.447N P=0.685N P=0.721N P=0.467N P=0.670N P=0.489 | |LOGISTIC REGRESSION| P=0.176 P=0.496N P=0.609 P=0.697 P=0.484N P=0.567 P=0.476 | |COCH-ARM / FISHERS | P=0.172 P=0.486N P=0.748N P=0.748N P=0.495N P=0.748 P=0.507 | |ORDER RESTRICTED | P=0.223 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 56 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/52 (6%) 1/55 (2%) 0/53 (0%) 1/53 (2%) 3/53 (6%) 2/51 (4%) 2/53 (4%) | |POLY-3 RATE (b) | 3/32.17 1/38.56 0/39.60 1/37.58 3/37.14 2/42.54 2/32.69 | |POLY-3 PERCENT (g) | 9.3% 2.6% 0.0% 2.7% 8.1% 4.7% 6.1% | |TERMINAL (d) | 1/15 (7%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 574 720 --- 658 618 320 603 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.270 P=0.180N P=0.066N P=0.217N P=0.578N P=0.338N P=0.568N | |POLY 3 | P=0.335 P=0.242N P=0.085N P=0.250N P=0.596N P=0.376N P=0.493N | |POLY 1.5 | P=0.362 P=0.260N P=0.095N P=0.262N P=0.617N P=0.419N P=0.485N | |POLY 6 | P=0.302 P=0.216N P=0.075N P=0.240N P=0.577N P=0.334N P=0.528N | |LOGISTIC REGRESSION| P=0.389 P=0.239N P=0.094N P=0.258N P=0.599N P=0.567N P=0.490N | |COCH-ARM / FISHERS | P=0.392 P=0.288N P=0.118N P=0.302N P=0.652N P=0.509N P=0.491N | |ORDER RESTRICTED | P=0.309N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 37/50 (74%) 34/52 (65%) 41/46 (89%) 45/48 (94%) 36/41 (88%) 47/49 (96%) 41/44 (93%) | |POLY-3 RATE (b) | 37/45.02 34/44.40 41/43.90 45/45.61 36/36.59 47/48.09 41/41.71 | |POLY-3 PERCENT (g) | 82.2% 76.6% 93.4% 98.7% 98.4% 97.7% 98.3% | |TERMINAL (d) | 9/15 (60%) 15/22 (68%) 19/21 (91%) 19/19 (100%) 14/14 (100%) 22/23 (96%) 7/7 (100%) | |FIRST INCIDENCE | 126 202 300 385 531 185 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.052N P=0.203N P=0.543N P=0.292N P=0.232N P=0.115 | |POLY 3 | P<0.001 ** P=0.340N P=0.088 P=0.005 ** P=0.014 * P=0.010 * P=0.010 * | |POLY 1.5 | P<0.001 ** P=0.297N P=0.063 P=0.005 ** P=0.018 * P=0.005 ** P=0.008 ** | |POLY 6 | P<0.001 ** P=0.376N P=0.117 P=0.006 ** P=0.013 * P=0.017 * P=0.012 * | |LOGISTIC REGRESSION| P<0.001 ** P=0.196N P=0.081 P=0.018 * P=0.168 P=0.009 ** P=0.016 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.233N P=0.050 P=0.008 ** P=0.082 P=0.002 ** P=0.012 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 57 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Thyroid Gland | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 1/55 (2%) 4/52 (8%) 0/51 (0%) 0/52 (0%) 0/50 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 0/31.37 1/38.53 4/39.64 0/36.51 0/35.79 0/41.02 0/29.95 | |POLY-3 PERCENT (g) | 0.0% 2.6% 10.1% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 3/26 (12%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 727 (T) 709 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.173N P=0.602 P=0.154 (e) (e) (e) (e) | |POLY 3 | P=0.076N P=0.541 P=0.095 (e) (e) (e) (e) | |POLY 1.5 | P=0.091N P=0.527 P=0.081 (e) (e) (e) (e) | |POLY 6 | P=0.068N P=0.561 P=0.114 (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.145N P=0.602 P=0.137 (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.126N P=0.514 P=0.059 (e) (e) (e) (e) | |ORDER RESTRICTED | P=0.207N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG 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%) 18/52 (35%) 16/50 (32%) 19/48 (40%) | |POLY-3 RATE (b) | 12/33.93 21/40.89 17/42.41 19/40.46 18/39.59 16/42.33 19/35.88 | |POLY-3 PERCENT (g) | 35.4% 51.4% 40.1% 47.0% 45.5% 37.8% 53.0% | |TERMINAL (d) | 5/15 (33%) 14/25 (56%) 10/26 (39%) 11/22 (50%) 6/16 (38%) 12/23 (52%) 2/7 (29%) | |FIRST INCIDENCE | 541 356 428 436 531 554 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.011 * P=0.427 P=0.463N P=0.384 P=0.321 P=0.412N P=0.036 * | |POLY 3 | P=0.288 P=0.115 P=0.426 P=0.212 P=0.255 P=0.508 P=0.096 | |POLY 1.5 | P=0.261 P=0.088 P=0.334 P=0.165 P=0.201 P=0.401 P=0.078 | |POLY 6 | P=0.285 P=0.169 P=0.532 P=0.260 P=0.320 P=0.586N P=0.108 | |LOGISTIC REGRESSION| P=0.195 P=0.152 P=0.399 P=0.180 P=0.229 P=0.591N P=0.066 | |COCH-ARM / FISHERS | P=0.205 P=0.069 P=0.191 P=0.088 P=0.140 P=0.216 P=0.058 | |ORDER RESTRICTED | P=0.129 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 58 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG 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%) 28/52 (54%) 26/50 (52%) 16/48 (33%) | |POLY-3 RATE (b) | 9/37.19 13/42.20 13/42.54 17/40.34 28/42.67 26/45.46 16/37.59 | |POLY-3 PERCENT (g) | 24.2% 30.8% 30.6% 42.2% 65.6% 57.2% 42.6% | |TERMINAL (d) | 2/15 (13%) 5/25 (20%) 6/26 (23%) 9/22 (41%) 12/16 (75%) 15/23 (65%) 2/7 (29%) | |FIRST INCIDENCE | 201 448 498 405 247 320 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.517 P=0.549 P=0.210 P=0.002 ** P=0.030 * P=0.053 | |POLY 3 | P=0.010 * P=0.341 P=0.350 P=0.069 P<0.001 ** P<0.001 ** P=0.066 | |POLY 1.5 | P=0.012 * P=0.292 P=0.294 P=0.059 P<0.001 ** P<0.001 ** P=0.064 | |POLY 6 | P=0.005 ** P=0.444 P=0.445 P=0.091 P<0.001 ** P=0.005 ** P=0.060 | |LOGISTIC REGRESSION| P=0.009 ** P=0.246 P=0.135 P=0.030 * P<0.001 ** P<0.001 ** P=0.025 * | |COCH-ARM / FISHERS | P=0.009 ** P=0.285 P=0.236 P=0.050 P<0.001 ** P<0.001 ** P=0.053 | |ORDER RESTRICTED | P=0.003 ** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Tooth: Peridontal Tissue | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/12 (83%) 12/12 (100%) 10/10 (100%) 9/9 (100%) 10/10 (100%) 8/9 (89%) 18/19 (95%) | |POLY-3 RATE (b) | 10/12.00 12/12.00 10/10.00 9/9.00 10/10.00 8/9.00 18/18.62 | |POLY-3 PERCENT (g) | 83.3% 100.0% 100.0% 100.0% 100.0% 88.9% 96.7% | |TERMINAL (d) | 5/7 (71%) 9/9 (100%) 5/5 (100%) 4/4 (100%) 4/4 (100%) 5/6 (83%) 4/4 (100%) | |FIRST INCIDENCE | 405 253 300 436 531 573 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.513N P=0.613 P=0.564 P=0.479 P=0.284N P=0.011 * | |POLY 3 | P=0.540 P=0.229 P=0.272 P=0.297 P=0.272 P=0.602 P=0.258 | |POLY 1.5 | P=0.594 P=0.229 P=0.272 P=0.297 P=0.272 P=0.602 P=0.294 | |POLY 6 | P=0.455 P=0.229 P=0.272 P=0.297 P=0.272 P=0.602 P=0.208 | |LOGISTIC REGRESSION| P=0.494N (e) (e) (e) (e) (e) P=0.450 | |COCH-ARM / FISHERS | P=0.580N P=0.239 P=0.286 P=0.314 P=0.286 P=0.612 P=0.328 | |ORDER RESTRICTED | P=0.024 * (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 59 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG 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%) 0/10 (0%) 1/9 (11%) 0/19 (0%) | |POLY-3 RATE (b) | 2/9.81 0/10.52 0/7.71 0/6.56 0/8.18 1/8.19 0/12.13 | |POLY-3 PERCENT (g) | 20.4% 0.0% 0.0% 0.0% 0.0% 12.2% 0.0% | |TERMINAL (d) | 2/7 (29%) 0/9 (0%) 0/5 (0%) 0/4 (0%) 0/4 (0%) 1/6 (17%) 0/4 (0%) | |FIRST INCIDENCE | 727 (T) --- --- --- --- 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.506N P=0.178N P=0.308N P=0.362N P=0.362N P=0.558N P=0.362N | |POLY 3 | P=0.345N P=0.210N P=0.283N P=0.324N P=0.268N P=0.566N P=0.174N | |POLY 1.5 | P=0.325N P=0.221N P=0.284N P=0.310N P=0.267N P=0.579N P=0.158N | |POLY 6 | P=0.410N P=0.196N P=0.277N P=0.346N P=0.277N P=0.553N P=0.202N | |LOGISTIC REGRESSION| P=0.506N (e) (e) (e) (e) P=0.558N (e) | |COCH-ARM / FISHERS | P=0.306N P=0.239N P=0.286N P=0.314N P=0.286N P=0.612N P=0.142N | |ORDER RESTRICTED | P=0.009N** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Ureter | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/3 (67%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 0/0.14 0/0.00 0/0.00 0/0.00 2/2.75 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 72.8% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- --- --- 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004 ** (e) (e) (e) (e) (e) P=0.233 | |POLY 3 | (e) (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.187 (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.282 (e) (e) (e) (e) (e) P=1.000 | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 60 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Ureter | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 1/1 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/3 (67%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 1/1.00 0/0.00 0/0.00 0/0.00 2/2.08 | |POLY-3 PERCENT (g) | 0.0% 0.0% 100.0% 0.0% 0.0% 0.0% 96.3% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 376 --- --- --- 588 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.274 (e) (e) (e) (e) (e) P=0.471 | |POLY 3 | (e) (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.500N (e) (e) (e) (e) (e) P=1.000 | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Ureter: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 1/1 (100%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 3/3 (100%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 1/1.00 0/0.00 0/0.00 0/0.00 3/3.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 100.0% 0.0% 0.0% 0.0% 100.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 376 --- --- --- 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 61 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Urinary Bladder | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/51 (8%) 6/54 (11%) 10/53 (19%) 6/52 (12%) 7/52 (13%) 4/52 (8%) 6/53 (11%) | |POLY-3 RATE (b) | 4/32.86 6/41.99 10/43.51 6/38.88 7/39.11 4/42.47 6/34.02 | |POLY-3 PERCENT (g) | 12.2% 14.3% 23.0% 15.4% 17.9% 9.4% 17.6% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 5/26 (19%) 1/22 (5%) 2/16 (13%) 1/23 (4%) 1/7 (14%) | |FIRST INCIDENCE | 391 350 188 448 301 573 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.491 P=0.496 P=0.216 P=0.526 P=0.356 P=0.423N P=0.274 | |POLY 3 | P=0.416N P=0.530 P=0.183 P=0.478 P=0.366 P=0.497N P=0.387 | |POLY 1.5 | P=0.400N P=0.479 P=0.146 P=0.451 P=0.331 P=0.543N P=0.402 | |POLY 6 | P=0.459N P=0.592 P=0.227 P=0.507 P=0.398 P=0.448N P=0.337 | |LOGISTIC REGRESSION| P=0.398N P=0.356 P=0.052 P=0.374 P=0.247 P=0.639 P=0.395 | |COCH-ARM / FISHERS | P=0.402N P=0.408 P=0.086 P=0.383 P=0.274 P=0.631N P=0.395 | |ORDER RESTRICTED | P=0.532 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG 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%) 1/52 (2%) 2/52 (4%) 2/53 (4%) | |POLY-3 RATE (b) | 1/31.35 1/38.94 1/40.46 2/37.45 1/36.79 2/41.91 2/32.25 | |POLY-3 PERCENT (g) | 3.2% 2.6% 2.5% 5.3% 2.7% 4.8% 6.2% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | 574 524 376 658 301 618 660 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.211 P=0.730N P=0.727N P=0.598 P=0.737N P=0.638 P=0.421 | |POLY 3 | P=0.248 P=0.711N P=0.701N P=0.562 P=0.725N P=0.599 P=0.510 | |POLY 1.5 | P=0.271 P=0.728N P=0.720N P=0.546 P=0.736N P=0.568 P=0.518 | |POLY 6 | P=0.222 P=0.687N P=0.680N P=0.577 P=0.716N P=0.631 P=0.481 | |LOGISTIC REGRESSION| P=0.295 P=0.761N P=0.709 P=0.531 P=0.741 P=0.540 P=0.510 | |COCH-ARM / FISHERS | P=0.291 P=0.738N P=0.743N P=0.507 P=0.748N P=0.507 P=0.515 | |ORDER RESTRICTED | P=0.477 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 62 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Adenomyosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 1/55 (2%) 0/53 (0%) 1/52 (2%) 0/53 (0%) 2/52 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.36 1/38.53 0/39.60 1/37.40 0/36.61 2/41.91 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 2.6% 0.0% 2.7% 0.0% 4.8% 0.0% | |TERMINAL (d) | 0/15 (0%) 1/25 (4%) 0/26 (0%) 0/22 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | --- 727 (T) --- 592 --- 618 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.503 P=0.602 (e) P=0.535 (e) P=0.344 (e) | |POLY 3 | P=0.481 P=0.541 (e) P=0.535 (e) P=0.307 (e) | |POLY 1.5 | P=0.533 P=0.527 (e) P=0.524 (e) P=0.281 (e) | |POLY 6 | P=0.416 P=0.561 (e) P=0.547 (e) P=0.338 (e) | |LOGISTIC REGRESSION| P=0.581 P=0.602 (e) P=0.496 (e) P=0.286 (e) | |COCH-ARM / FISHERS | P=0.588 P=0.514 (e) P=0.500 (e) P=0.248 (e) | |ORDER RESTRICTED | P=0.392 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/55 (0%) 0/53 (0%) 1/52 (2%) 2/53 (4%) 1/52 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 0/31.36 0/38.53 0/39.60 1/37.44 2/36.91 1/42.13 1/32.01 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.7% 5.4% 2.4% 3.1% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 0/22 (0%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- 576 645 535 700 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.150 (e) (e) P=0.534 P=0.275 P=0.552 P=0.413 | |POLY 3 | P=0.183 (e) (e) P=0.535 P=0.274 P=0.558 P=0.504 | |POLY 1.5 | P=0.203 (e) (e) P=0.524 P=0.261 P=0.537 P=0.507 | |POLY 6 | P=0.163 (e) (e) P=0.547 P=0.288 P=0.580 P=0.490 | |LOGISTIC REGRESSION| P=0.217 (e) (e) P=0.487 P=0.278 P=0.442 P=0.456 | |COCH-ARM / FISHERS | P=0.222 (e) (e) P=0.500 P=0.252 P=0.500 P=0.505 | |ORDER RESTRICTED | P=0.311 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 63 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/52 (23%) 12/55 (22%) 11/53 (21%) 16/52 (31%) 10/53 (19%) 6/52 (12%) 4/53 (8%) | |POLY-3 RATE (b) | 12/35.65 12/42.38 11/42.96 16/40.30 10/39.29 6/42.51 4/33.98 | |POLY-3 PERCENT (g) | 33.7% 28.3% 25.6% 39.7% 25.5% 14.1% 11.8% | |TERMINAL (d) | 2/15 (13%) 4/25 (16%) 4/26 (15%) 9/22 (41%) 3/16 (19%) 4/23 (17%) 0/7 (0%) | |FIRST INCIDENCE | 391 328 188 448 331 535 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.026N* P=0.257N P=0.194N P=0.558 P=0.264N P=0.018N* P=0.065N | |POLY 3 | P=0.003N** P=0.395N P=0.296N P=0.377 P=0.296N P=0.035N* P=0.025N* | |POLY 1.5 | P=0.003N** P=0.445N P=0.350N P=0.348 P=0.319N P=0.049N* P=0.021N* | |POLY 6 | P=0.007N** P=0.341N P=0.244N P=0.391 P=0.298N P=0.027N* P=0.042N* | |LOGISTIC REGRESSION| P=0.003N** P=0.507N P=0.452N P=0.351 P=0.344N P=0.064N P=0.025N* | |COCH-ARM / FISHERS | P=0.003N** P=0.530N P=0.479N P=0.254 P=0.386N P=0.097N P=0.025N* | |ORDER RESTRICTED | P=0.033N* (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/55 (0%) 0/53 (0%) 2/52 (4%) 1/53 (2%) 1/52 (2%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.36 0/38.53 0/39.60 2/36.94 1/36.84 1/41.58 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.4% 2.7% 2.4% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 0/26 (0%) 2/22 (9%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- 727 (T) 665 714 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.519 (e) (e) P=0.325 P=0.555 P=0.624 (e) | |POLY 3 | P=0.577 (e) (e) P=0.274 P=0.532 P=0.555 (e) | |POLY 1.5 | P=0.617 (e) (e) P=0.263 P=0.521 P=0.536 (e) | |POLY 6 | P=0.521 (e) (e) P=0.286 P=0.543 P=0.576 (e) | |LOGISTIC REGRESSION| P=0.602 (e) (e) P=0.325 P=0.528 P=0.599 (e) | |COCH-ARM / FISHERS | P=0.617N (e) (e) P=0.248 P=0.505 P=0.500 (e) | |ORDER RESTRICTED | P=0.391 (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 64 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 26/52 (50%) 33/55 (60%) 25/53 (47%) 28/52 (54%) 29/53 (55%) 27/52 (52%) 11/53 (21%) | |POLY-3 RATE (b) | 26/41.07 33/47.72 25/45.60 28/45.56 29/45.96 27/46.70 11/35.60 | |POLY-3 PERCENT (g) | 63.3% 69.2% 54.8% 61.5% 63.1% 57.8% 30.9% | |TERMINAL (d) | 7/15 (47%) 16/25 (64%) 11/26 (42%) 12/22 (55%) 8/16 (50%) 12/23 (52%) 2/7 (29%) | |FIRST INCIDENCE | 321 253 188 385 247 440 555 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.050N P=0.391N P=0.073N P=0.291N P=0.476N P=0.098N P=0.023N* | |POLY 3 | P<0.001N** P=0.356 P=0.275N P=0.518N P=0.583N P=0.377N P=0.002N** | |POLY 1.5 | P<0.001N** P=0.306 P=0.313N P=0.557N P=0.545 P=0.449N P<0.001N** | |POLY 6 | P=0.008N** P=0.379 P=0.246N P=0.523N P=0.582N P=0.329N P=0.010N* | |LOGISTIC REGRESSION| P<0.001N** P=0.240 P=0.362N P=0.494 P=0.433 P=0.490N P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P=0.199 P=0.462N P=0.422 P=0.387 P=0.500 P=0.002N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 30 NG/KG 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/55 (0%) 2/53 (4%) 0/52 (0%) 0/53 (0%) 0/52 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.36 0/38.53 2/39.98 0/36.94 0/36.61 0/41.53 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 0.0% 5.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/25 (0%) 1/26 (4%) 0/22 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 621 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.397N (e) P=0.351 (e) (e) (e) (e) | |POLY 3 | P=0.265N (e) P=0.294 (e) (e) (e) (e) | |POLY 1.5 | P=0.295N (e) P=0.274 (e) (e) (e) (e) | |POLY 6 | P=0.260N (e) P=0.321 (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.347N (e) P=0.285 (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.343N (e) P=0.252 (e) (e) (e) (e) | |ORDER RESTRICTED | P=0.414N (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 65 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 100 175 300 550 1000 | | | NG/KG NG/KG NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 23/52 (44%) 33/55 (60%) 28/53 (53%) 24/52 (46%) 26/53 (49%) 32/52 (62%) 9/53 (17%) | |POLY-3 RATE (b) | 23/35.31 33/43.07 28/43.94 24/42.67 26/41.15 32/45.02 9/34.37 | |POLY-3 PERCENT (g) | 65.1% 76.6% 63.7% 56.3% 63.2% 71.1% 26.2% | |TERMINAL (d) | 12/15 (80%) 22/25 (88%) 16/26 (62%) 11/22 (50%) 12/16 (75%) 21/23 (91%) 3/7 (43%) | |FIRST INCIDENCE | 496 350 188 385 403 327 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.169N P=0.438N P=0.161N P=0.194N P=0.537N P=0.369N P=0.065N | |POLY 3 | P<0.001N** P=0.165 P=0.545N P=0.273N P=0.527N P=0.361 P<0.001N** | |POLY 1.5 | P<0.001N** P=0.107 P=0.497 P=0.391N P=0.560 P=0.213 P<0.001N** | |POLY 6 | P=0.003N** P=0.288 P=0.371N P=0.181N P=0.434N P=0.543 P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P=0.187 P=0.556N P=0.389N P=0.504N P=0.493 P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P=0.075 P=0.246 P=0.500 P=0.382 P=0.058 P=0.002N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) (e) (e) | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Number of tumor-bearing animals / Poly-3 number (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers exact tests compare directly the overall incidence rates For all tests a negative trend is indicated by N (e) Value of Statistic cannot be computed. (g) Poly-3 adjusted lifetime tumor incidence. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).