TDMS Study 05161-05 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst RIDDELLIINE DATE: 12/15/00 EXPERIMENT: 05161 TEST: 05 TIME: 12:16:38 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-55393 ROUTE: GAVAGE NTP C#: 61358C PATHOLOGIST: HEATH, JAMES E. CAS: 23246-96-0 ------------------------------------------------------------------------------------------------------------------------------------ RATS/FINAL#1_FEMALES REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 003 0 MG/KG/DY INCLUDE 004 0.01 MG/KG/DY INCLUDE 005 0.033 MG/KG/DY INCLUDE 006 0.1 MG/KG/DY INCLUDE 007 0.33 MG/KG/DY INCLUDE 008 1.0 MG/KG/DY NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst RIDDELLIINE DATE: 12/15/00 EXPERIMENT: 05161 TEST: 05 TIME: 12:16:38 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-55393 ROUTE: GAVAGE NTP C#: 61358C PATHOLOGIST: HEATH, JAMES E. CAS: 23246-96-0 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF RIDDELLIINE =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Accessory Adrenal Cortical Nodule Degeneration Fatty Hyperplasia Focal Hypertrophy Focal Bone Marrow Hyperplasia Bone: Cranium Osteopetrosis Bone: Femur Osteopetrosis Brain Compression Hydrocephalus Clitoral Gland Cyst Hyperplasia Inflammation Chronic Heart Cardiomyopathy Kidney Nephropathy Kidney: Renal Tubule Hyaline Droplet Necrosis Pigmentation Kidney: Transitional Epithelium Hyperplasia Liver Angiectasis Basophilic Focus Clear Cell Focus Eosinophilic Focus Hematopoietic Cell Proliferation Hemorrhage Hepatodiaphragmatic Nodule Infiltration Cellular Mixed Cell Mixed Cell Focus Necrosis Focal Liver: Bile Duct Hyperplasia Liver: Hepatocyte Cytomegaly Hyperplasia Regenerative Vacuolization Cytoplasmic Liver: Kupffer Cell Pigmentation Lung Congestion Edema Hemorrhage Infiltration Cellular Histiocyte Lung: Alveolar Epithelium Hyperplasia Lymph Node, Mandibular Pigmentation Lymph Node, Mediastinal Congestion Hemorrhage Pigmentation Lymph Node, Mesenteric Hemorrhage Pigmentation Lymph Node: Pancreatic Hemorrhage Pigmentation Lymph Node: Renal Pigmentation Mammary Gland Hyperplasia NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst RIDDELLIINE DATE: 12/15/00 EXPERIMENT: 05161 TEST: 05 TIME: 12:16:38 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-55393 ROUTE: GAVAGE NTP C#: 61358C PATHOLOGIST: HEATH, JAMES E. CAS: 23246-96-0 Mesentery: Fat Necrosis Nose: Respiratory Epithelium Hyperplasia Ovary Cyst Pancreas Atrophy Pituitary Gland: Pars Distalis Angiectasis Cyst Hyperplasia Focal Salivary Glands Atrophy Skeletal Muscle Hemorrhage Spleen Congestion Hematopoietic Cell Proliferation Pigmentation Stomach, Forestomach: Epithelium Hyperplasia Stomach, Glandular Erosion Ulcer Thymus Hemorrhage Thyroid Gland Ultimobranchial Cyst Thyroid Gland: C-Cell Hyperplasia Uterus Hydrometra Hyperplasia Cystic =============================================================== Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex | | Accessory Adrenal Cortical Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/50 (12%) 2/50 (4%) 6/50 (12%) 4/50 (8%) 2/50 (4%) 7/50 (14%) | |POLY-3 RATE (b) | 6/44.74 2/40.06 6/42.82 4/41.17 2/41.99 7/21.99 | |POLY-3 PERCENT (g) | 13.4% 5.0% 14.0% 9.7% 4.8% 31.8% | |TERMINAL (d) | 2/33 (6%) 1/22 (5%) 3/28 (11%) 2/22 (9%) 2/29 (7%) 0/0 (0%) | |FIRST INCIDENCE | 437 698 571 646 729 (T) 426 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.229N P=0.560 P=0.512N P=0.169N P=0.005 ** | |POLY 3 | P=0.085 P=0.170N P=0.590 P=0.422N P=0.153N P=0.092 | |POLY 1.5 | P=0.117 P=0.153N P=0.604 P=0.404N P=0.143N P=0.228 | |POLY 6 | P=0.107 P=0.200N P=0.568 P=0.452N P=0.172N P=0.023 * | |LOGISTIC REGRESSION| P=0.338 P=0.117N P=0.616N P=0.348N P=0.137N P=0.470N | |COCH-ARM / FISHERS | P=0.228 P=0.134N P=0.620N P=0.370N P=0.134N P=0.500 | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex | | Degeneration Fatty | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/50 (18%) 9/50 (18%) 12/50 (24%) 8/50 (16%) 13/50 (26%) 3/50 (6%) | |POLY-3 RATE (b) | 9/43.20 9/40.47 12/43.77 8/41.95 13/44.52 3/18.97 | |POLY-3 PERCENT (g) | 20.8% 22.2% 27.4% 19.1% 29.2% 15.8% | |TERMINAL (d) | 8/33 (24%) 7/22 (32%) 7/28 (25%) 4/22 (18%) 7/29 (24%) 0/0 (0%) | |FIRST INCIDENCE | 640 573 437 451 451 527 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.025 * P=0.272 P=0.214 P=0.426 P=0.172 P=0.002 ** | |POLY 3 | P=0.519 P=0.544 P=0.320 P=0.527N P=0.254 P=0.461N | |POLY 1.5 | P=0.249N P=0.573 P=0.321 P=0.518N P=0.251 P=0.220N | |POLY 6 | P=0.246 P=0.491 P=0.309 P=0.550N P=0.247 P=0.443 | |LOGISTIC REGRESSION| P=0.347N P=0.453 P=0.300 P=0.543N P=0.232 P=0.304 | |COCH-ARM / FISHERS | P=0.033N* P=0.602N P=0.312 P=0.500N P=0.235 P=0.061N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 3/50 (6%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/42.87 0/39.94 3/43.16 1/40.87 0/41.99 0/17.60 | |POLY-3 PERCENT (g) | 0.0% 0.0% 7.0% 2.5% 0.0% 0.0% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 437 707 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.496N (e) P=0.124 P=0.455 (e) (e) | |POLY 3 | P=0.299N (e) P=0.119 P=0.490 (e) (e) | |POLY 1.5 | P=0.288N (e) P=0.120 P=0.494 (e) (e) | |POLY 6 | P=0.355N (e) P=0.117 P=0.484 (e) (e) | |LOGISTIC REGRESSION| P=0.135N (e) P=0.090 P=0.487 (e) (e) | |COCH-ARM / FISHERS | P=0.263N (e) P=0.121 P=0.500 (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 5/50 (10%) 6/50 (12%) 4/50 (8%) 9/50 (18%) 3/50 (6%) | |POLY-3 RATE (b) | 4/43.99 5/40.06 6/42.38 4/41.21 9/42.53 3/19.64 | |POLY-3 PERCENT (g) | 9.1% 12.5% 14.2% 9.7% 21.2% 15.3% | |TERMINAL (d) | 2/33 (6%) 4/22 (18%) 5/28 (18%) 2/22 (9%) 7/29 (24%) 0/0 (0%) | |FIRST INCIDENCE | 437 698 444 668 630 407 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** P=0.315 P=0.302 P=0.513 P=0.088 P=0.148 | |POLY 3 | P=0.166 P=0.441 P=0.345 P=0.607 P=0.100 P=0.399 | |POLY 1.5 | P=0.401 P=0.468 P=0.359 P=0.619 P=0.108 P=0.584 | |POLY 6 | P=0.051 P=0.400 P=0.321 P=0.588 P=0.087 P=0.210 | |LOGISTIC REGRESSION| P=0.388 P=0.487 P=0.374 P=0.638N P=0.116 P=0.285N | |COCH-ARM / FISHERS | P=0.363N P=0.500 P=0.370 P=0.643N P=0.117 P=0.500N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/50 (18%) 5/50 (10%) 7/50 (14%) 2/50 (4%) 4/50 (8%) 2/50 (4%) | |POLY-3 RATE (b) | 9/43.90 5/40.30 7/42.69 2/41.55 4/42.52 2/18.45 | |POLY-3 PERCENT (g) | 20.5% 12.4% 16.4% 4.8% 9.4% 10.8% | |TERMINAL (d) | 7/33 (21%) 3/22 (14%) 4/28 (14%) 1/22 (5%) 1/29 (3%) 0/0 (0%) | |FIRST INCIDENCE | 483 643 532 451 671 528 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.369 P=0.416N P=0.498N P=0.079N P=0.170N P=0.157 | |POLY 3 | P=0.203N P=0.240N P=0.415N P=0.030N* P=0.125N P=0.319N | |POLY 1.5 | P=0.136N P=0.218N P=0.403N P=0.029N* P=0.120N P=0.123N | |POLY 6 | P=0.231N P=0.281N P=0.438N P=0.035N* P=0.137N P=0.588 | |LOGISTIC REGRESSION| P=0.188N P=0.230N P=0.399N P=0.027N* P=0.119N P=0.528N | |COCH-ARM / FISHERS | P=0.051N P=0.194N P=0.393N P=0.026N* P=0.117N P=0.026N* | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 3/49 (6%) 0/50 (0%) 3/50 (6%) 3/50 (6%) 0/50 (0%) | |POLY-3 RATE (b) | 1/42.87 3/40.69 0/41.60 3/41.16 3/42.15 0/17.60 | |POLY-3 PERCENT (g) | 2.3% 7.4% 0.0% 7.3% 7.1% 0.0% | |TERMINAL (d) | 1/33 (3%) 1/22 (5%) 0/28 (0%) 1/22 (5%) 2/29 (7%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 407 --- 651 686 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.615 P=0.239 P=0.533N P=0.219 P=0.263 P=1.000N | |POLY 3 | P=0.535 P=0.286 P=0.506N P=0.290 P=0.299 P=0.650N | |POLY 1.5 | P=0.431N P=0.293 P=0.503N P=0.295 P=0.304 P=0.586N | |POLY 6 | P=0.314 P=0.272 P=0.513N P=0.281 P=0.288 P=0.716N | |LOGISTIC REGRESSION| P=0.307N P=0.329 (e) P=0.284 P=0.275 (e) | |COCH-ARM / FISHERS | P=0.233N P=0.301 P=0.500N P=0.309 P=0.309 P=0.500N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/50 (12%) 3/50 (6%) 8/50 (16%) 7/50 (14%) 10/50 (20%) 32/50 (64%) | |POLY-3 RATE (b) | 6/45.97 3/41.67 8/43.74 7/42.19 10/44.09 32/38.51 | |POLY-3 PERCENT (g) | 13.1% 7.2% 18.3% 16.6% 22.7% 83.1% | |TERMINAL (d) | 1/33 (3%) 0/22 (0%) 3/28 (11%) 3/22 (14%) 4/29 (14%) 0/0 (0%) | |FIRST INCIDENCE | 393 407 437 307 524 350 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.297N P=0.352 P=0.361 P=0.191 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.292N P=0.348 P=0.434 P=0.178 P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.271N P=0.364 P=0.457 P=0.190 P<0.001 ** | |POLY 6 | P<0.001 ** P=0.325N P=0.328 P=0.401 P=0.165 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.152N P=0.376 P=0.603 P=0.175 P=0.046 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.243N P=0.387 P=0.500 P=0.207 P<0.001 ** | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Bone: Cranium | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/50 (20%) 10/50 (20%) 12/50 (24%) 6/50 (12%) 7/50 (14%) 0/50 (0%) | |POLY-3 RATE (b) | 10/43.13 10/41.68 12/42.66 6/40.84 7/42.15 0/17.60 | |POLY-3 PERCENT (g) | 23.2% 24.0% 28.1% 14.7% 16.6% 0.0% | |TERMINAL (d) | 7/33 (21%) 5/22 (23%) 8/28 (29%) 5/22 (23%) 6/29 (21%) 0/0 (0%) | |FIRST INCIDENCE | 693 573 616 715 686 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.211N P=0.304 P=0.270 P=0.502N P=0.412N P=1.000N | |POLY 3 | P=0.030N* P=0.567 P=0.390 P=0.237N P=0.312N P=0.057N | |POLY 1.5 | P=0.007N** P=0.583 P=0.400 P=0.226N P=0.301N P=0.010N* | |POLY 6 | P=0.104N P=0.535 P=0.369 P=0.262N P=0.339N P=0.270N | |LOGISTIC REGRESSION| P=0.058N P=0.525 P=0.339 P=0.353N P=0.381N P=0.764N | |COCH-ARM / FISHERS | P<0.001N** P=0.598N P=0.405 P=0.207N P=0.298N P<0.001N** | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Bone: Femur | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/50 (24%) 7/50 (14%) 9/50 (18%) 15/50 (30%) 14/50 (28%) 9/50 (18%) | |POLY-3 RATE (b) | 12/44.10 7/40.61 9/42.66 15/42.67 14/43.45 9/23.00 | |POLY-3 PERCENT (g) | 27.2% 17.2% 21.1% 35.2% 32.2% 39.1% | |TERMINAL (d) | 8/33 (24%) 3/22 (14%) 5/28 (18%) 9/22 (41%) 9/29 (31%) 0/0 (0%) | |FIRST INCIDENCE | 498 600 616 552 587 461 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.399N P=0.445N P=0.097 P=0.303 P<0.001 ** | |POLY 3 | P=0.073 P=0.199N P=0.339N P=0.284 P=0.389 P=0.250 | |POLY 1.5 | P=0.239 P=0.177N P=0.324N P=0.296 P=0.403 P=0.528 | |POLY 6 | P=0.018 * P=0.242N P=0.366N P=0.260 P=0.363 P=0.059 | |LOGISTIC REGRESSION| P=0.076 P=0.194N P=0.329N P=0.288 P=0.392 P=0.415 | |COCH-ARM / FISHERS | P=0.441N P=0.154N P=0.312N P=0.326 P=0.410 P=0.312N | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Brain | | Compression | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/50 (18%) 11/50 (22%) 15/50 (30%) 6/50 (12%) 12/50 (24%) 2/50 (4%) | |POLY-3 RATE (b) | 9/43.90 11/41.42 15/43.64 6/41.57 12/42.80 2/18.40 | |POLY-3 PERCENT (g) | 20.5% 26.6% 34.4% 14.4% 28.0% 10.9% | |TERMINAL (d) | 4/33 (12%) 7/22 (32%) 8/28 (29%) 2/22 (9%) 9/29 (31%) 0/0 (0%) | |FIRST INCIDENCE | 545 520 518 664 570 552 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.129 P=0.171 P=0.081 P=0.497N P=0.225 P=0.067 | |POLY 3 | P=0.286N P=0.342 P=0.109 P=0.326N P=0.284 P=0.320N | |POLY 1.5 | P=0.081N P=0.371 P=0.116 P=0.313N P=0.301 P=0.124N | |POLY 6 | P=0.485 P=0.293 P=0.096 P=0.350N P=0.251 P=0.584 | |LOGISTIC REGRESSION| P=0.246N P=0.357 P=0.114 P=0.313N P=0.288 P=0.646N | |COCH-ARM / FISHERS | P=0.006N** P=0.402 P=0.121 P=0.288N P=0.312 P=0.026N* | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Brain | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 0/50 (0%) 3/50 (6%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/42.87 1/40.38 0/41.60 3/41.98 0/41.99 0/17.60 | |POLY-3 PERCENT (g) | 2.3% 2.5% 0.0% 7.2% 0.0% 0.0% | |TERMINAL (d) | 1/33 (3%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 600 --- 561 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.600N P=0.713 P=0.533N P=0.274 P=0.526N P=1.000N | |POLY 3 | P=0.311N P=0.748 P=0.506N P=0.297 P=0.504N P=0.650N | |POLY 1.5 | P=0.281N P=0.754 P=0.503N P=0.299 P=0.501N P=0.586N | |POLY 6 | P=0.390N P=0.736 P=0.513N P=0.292 P=0.511N P=0.716N | |LOGISTIC REGRESSION| P=0.158N P=0.759N (e) P=0.325 (e) (e) | |COCH-ARM / FISHERS | P=0.230N P=0.753N P=0.500N P=0.309 P=0.500N P=0.500N | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Brain | | Hydrocephalus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 4/50 (8%) 8/50 (16%) 1/50 (2%) 10/50 (20%) 3/50 (6%) | |POLY-3 RATE (b) | 3/43.63 4/39.94 8/42.32 1/40.98 10/42.80 3/18.82 | |POLY-3 PERCENT (g) | 6.9% 10.0% 18.9% 2.4% 23.4% 15.9% | |TERMINAL (d) | 0/33 (0%) 4/22 (18%) 4/28 (14%) 0/22 (0%) 7/29 (24%) 0/0 (0%) | |FIRST INCIDENCE | 545 729 (T) 591 678 570 552 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.330 P=0.076 P=0.374N P=0.028 * P=0.004 ** | |POLY 3 | P=0.078 P=0.452 P=0.087 P=0.328N P=0.030 * P=0.289 | |POLY 1.5 | P=0.266 P=0.475 P=0.093 P=0.320N P=0.033 * P=0.452 | |POLY 6 | P=0.015 * P=0.414 P=0.077 P=0.342N P=0.025 * P=0.148 | |LOGISTIC REGRESSION| P=0.045 * P=0.466 P=0.097 P=0.294N P=0.036 * P=0.374 | |COCH-ARM / FISHERS | P=0.482N P=0.500 P=0.100 P=0.309N P=0.036 * P=0.661N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Clitoral Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/49 (10%) 2/49 (4%) 3/49 (6%) 1/48 (2%) 4/49 (8%) 3/50 (6%) | |POLY-3 RATE (b) | 5/42.09 2/39.53 3/41.12 1/40.25 4/41.85 3/19.08 | |POLY-3 PERCENT (g) | 11.9% 5.1% 7.3% 2.5% 9.6% 15.7% | |TERMINAL (d) | 4/33 (12%) 2/22 (9%) 3/28 (11%) 0/22 (0%) 2/29 (7%) 0/0 (0%) | |FIRST INCIDENCE | 693 729 (T) 729 (T) 646 658 552 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.393N P=0.448N P=0.189N P=0.581N P<0.001 ** | |POLY 3 | P=0.226 P=0.241N P=0.368N P=0.111N P=0.504N P=0.499 | |POLY 1.5 | P=0.341 P=0.229N P=0.361N P=0.109N P=0.499N P=0.585N | |POLY 6 | P=0.213 P=0.265N P=0.386N P=0.116N P=0.518N P=0.266 | |LOGISTIC REGRESSION| P=0.063 P=0.314N P=0.413N P=0.117N P=0.526N P=0.227 | |COCH-ARM / FISHERS | P=0.573 P=0.218N P=0.357N P=0.107N P=0.500N P=0.346N | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Clitoral Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/49 (6%) 5/49 (10%) 4/49 (8%) 2/48 (4%) 2/49 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 3/41.95 5/39.88 4/41.43 2/40.53 2/42.02 0/17.60 | |POLY-3 PERCENT (g) | 7.2% 12.5% 9.7% 4.9% 4.8% 0.0% | |TERMINAL (d) | 3/33 (9%) 3/22 (14%) 3/28 (11%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 650 647 638 602 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.350N P=0.182 P=0.423 P=0.607N P=0.553N P=1.000N | |POLY 3 | P=0.119N P=0.328 P=0.493 P=0.516N P=0.499N P=0.336N | |POLY 1.5 | P=0.076N P=0.342 P=0.498 P=0.514N P=0.497N P=0.215N | |POLY 6 | P=0.177N P=0.303 P=0.481 P=0.524N P=0.507N P=0.511N | |LOGISTIC REGRESSION| P=0.117N P=0.268 P=0.465 P=0.519N P=0.503N (e) | |COCH-ARM / FISHERS | P=0.031N* P=0.357 P=0.500 P=0.510N P=0.500N P=0.117N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/49 (8%) 5/49 (10%) 4/49 (8%) 3/48 (6%) 4/49 (8%) 0/50 (0%) | |POLY-3 RATE (b) | 4/42.79 5/39.82 4/41.40 3/40.76 4/42.59 0/17.60 | |POLY-3 PERCENT (g) | 9.4% 12.6% 9.7% 7.4% 9.4% 0.0% | |TERMINAL (d) | 3/33 (9%) 4/22 (18%) 3/28 (11%) 0/22 (0%) 1/29 (3%) 0/0 (0%) | |FIRST INCIDENCE | 393 650 654 646 576 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.483N P=0.296 P=0.568 P=0.602N P=0.599 P=0.508N | |POLY 3 | P=0.227N P=0.455 P=0.626 P=0.527N P=0.641 P=0.262N | |POLY 1.5 | P=0.115N P=0.475 P=0.634 P=0.523N P=0.643 P=0.141N | |POLY 6 | P=0.410N P=0.422 P=0.611 P=0.536N P=0.635 P=0.460N | |LOGISTIC REGRESSION| P=0.060N P=0.491 P=0.643N P=0.494N P=0.629 P=0.072N | |COCH-ARM / FISHERS | P=0.033N* P=0.500 P=0.643N P=0.512N P=0.643N P=0.056N | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Esophagus | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 2/50 (4%) 0/48 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/40.87 2/40.76 0/40.38 0/40.79 0/41.25 0/17.60 | |POLY-3 PERCENT (g) | 0.0% 4.9% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/31 (0%) 0/22 (0%) 0/27 (0%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 612 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.731N P=0.232 (e) (e) (e) (e) | |POLY 3 | P=0.335N P=0.236 (e) (e) (e) (e) | |POLY 1.5 | P=0.366N P=0.241 (e) (e) (e) (e) | |POLY 6 | P=0.372N P=0.227 (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.294N P=0.263 (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.389N P=0.258 (e) (e) (e) (e) | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/50 (24%) 15/50 (30%) 8/50 (16%) 13/50 (26%) 8/50 (16%) 6/50 (12%) | |POLY-3 RATE (b) | 12/43.15 15/42.04 8/42.59 13/42.47 8/42.25 6/20.84 | |POLY-3 PERCENT (g) | 27.8% 35.7% 18.8% 30.6% 18.9% 28.8% | |TERMINAL (d) | 11/33 (33%) 8/22 (36%) 6/28 (21%) 7/22 (32%) 7/29 (24%) 0/0 (0%) | |FIRST INCIDENCE | 654 519 572 561 658 440 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.076 P=0.346N P=0.188 P=0.321N P<0.001 ** | |POLY 3 | P=0.337N P=0.290 P=0.230N P=0.481 P=0.236N P=0.578 | |POLY 1.5 | P=0.178N P=0.308 P=0.226N P=0.482 P=0.228N P=0.338N | |POLY 6 | P=0.484N P=0.257 P=0.246N P=0.472 P=0.260N P=0.229 | |LOGISTIC REGRESSION| P=0.540 P=0.232 P=0.264N P=0.430 P=0.300N P=0.176 | |COCH-ARM / FISHERS | P=0.035N* P=0.326 P=0.227N P=0.500 P=0.227N P=0.096N | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 32/50 (64%) 32/50 (64%) 33/50 (66%) 30/50 (60%) 38/50 (76%) 28/50 (56%) | |POLY-3 RATE (b) | 32/46.45 32/44.61 33/46.14 30/42.81 38/47.48 28/34.74 | |POLY-3 PERCENT (g) | 68.9% 71.7% 71.5% 70.1% 80.0% 80.6% | |TERMINAL (d) | 24/33 (73%) 19/22 (86%) 21/28 (75%) 20/22 (91%) 24/29 (83%) 0/0 (0%) | |FIRST INCIDENCE | 393 407 437 561 463 350 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.055 P=0.234 P=0.096 P=0.072 P<0.001 ** | |POLY 3 | P=0.089 P=0.471 P=0.479 P=0.545 P=0.147 P=0.153 | |POLY 1.5 | P=0.334 P=0.526 P=0.495 P=0.565N P=0.145 P=0.461 | |POLY 6 | P=0.013 * P=0.373 P=0.443 P=0.442 P=0.142 P=0.019 * | |LOGISTIC REGRESSION| P=0.028 * P=0.507 P=0.482 P=0.508N P=0.134 P=0.245 | |COCH-ARM / FISHERS | P=0.239N P=0.582N P=0.500 P=0.418N P=0.138 P=0.270N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 0/50 (0%) 2/50 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 0/42.87 1/40.13 2/42.39 0/40.79 2/43.49 1/18.44 | |POLY-3 PERCENT (g) | 0.0% 2.5% 4.7% 0.0% 4.6% 5.4% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 1/28 (4%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 679 437 --- 451 400 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.328 P=0.457 P=0.224 (e) P=0.247 P=0.492 | |POLY 3 | P=0.225 P=0.487 P=0.234 (e) P=0.240 P=0.354 | |POLY 1.5 | P=0.341 P=0.493 P=0.237 (e) P=0.241 P=0.417 | |POLY 6 | P=0.189 P=0.476 P=0.228 (e) P=0.236 P=0.288 | |LOGISTIC REGRESSION| P=0.328N P=0.498 P=0.217 (e) P=0.053 P=0.894 | |COCH-ARM / FISHERS | P=0.533 P=0.500 P=0.247 (e) P=0.247 P=0.500 | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 33/50 (66%) 23/50 (46%) 30/50 (60%) 26/50 (52%) 26/50 (52%) 9/50 (18%) | |POLY-3 RATE (b) | 33/44.89 23/41.49 30/43.44 26/43.64 26/43.29 9/22.68 | |POLY-3 PERCENT (g) | 73.5% 55.4% 69.1% 59.6% 60.1% 39.7% | |TERMINAL (d) | 28/33 (85%) 19/22 (86%) 23/28 (82%) 17/22 (77%) 22/29 (76%) 0/0 (0%) | |FIRST INCIDENCE | 393 407 532 307 587 400 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.589 P=0.443 P=0.353 P=0.289N P<0.001 ** | |POLY 3 | P=0.023N* P=0.048N* P=0.403N P=0.108N P=0.115N P=0.004N** | |POLY 1.5 | P<0.001N** P=0.039N* P=0.372N P=0.115N P=0.110N P<0.001N** | |POLY 6 | P=0.219N P=0.074N P=0.461N P=0.099N P=0.134N P=0.240N | |LOGISTIC REGRESSION| P=0.518 P=0.072N P=0.424N P=0.145N P=0.126N P=0.307N | |COCH-ARM / FISHERS | P<0.001N** P=0.035N* P=0.339N P=0.111N P=0.111N P<0.001N** | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) 1/50 (2%) 6/50 (12%) | |POLY-3 RATE (b) | 0/42.87 0/39.94 0/41.60 1/40.87 1/42.62 6/21.40 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.5% 2.4% 28.0% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- 707 524 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P=0.455 P=0.513 P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P=0.490 P=0.499 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P=0.494 P=0.500 P=0.004 ** | |POLY 6 | P<0.001 ** (e) (e) P=0.484 P=0.494 P<0.001 ** | |LOGISTIC REGRESSION| P=0.007 ** (e) (e) P=0.487 P=0.416 P=0.099 | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.500 P=0.500 P=0.013 * | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 38/50 (76%) 28/50 (56%) 31/50 (62%) 31/50 (62%) 41/50 (82%) 23/50 (46%) | |POLY-3 RATE (b) | 38/46.67 28/41.67 31/44.23 31/44.46 41/47.58 23/31.54 | |POLY-3 PERCENT (g) | 81.4% 67.2% 70.1% 69.7% 86.2% 72.9% | |TERMINAL (d) | 29/33 (88%) 21/22 (96%) 21/28 (75%) 18/22 (82%) 26/29 (90%) 0/0 (0%) | |FIRST INCIDENCE | 393 573 532 307 451 400 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.486 P=0.405N P=0.322 P=0.132 P<0.001 ** | |POLY 3 | P=0.336 P=0.077N P=0.136N P=0.129N P=0.354 P=0.241N | |POLY 1.5 | P=0.330N P=0.047N* P=0.115N P=0.121N P=0.339 P=0.034N* | |POLY 6 | P=0.066 P=0.165N P=0.178N P=0.145N P=0.363 P=0.482 | |LOGISTIC REGRESSION| P=0.019 * P=0.050N P=0.102N P=0.128N P=0.312 P=0.561N | |COCH-ARM / FISHERS | P=0.024N* P=0.028N* P=0.097N P=0.097N P=0.312 P=0.002N** | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Kidney: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 1/50 (2%) 1/50 (2%) 0/50 (0%) 5/50 (10%) | |POLY-3 RATE (b) | 1/42.87 1/39.94 1/41.91 1/41.33 0/41.99 5/20.21 | |POLY-3 PERCENT (g) | 2.3% 2.5% 2.4% 2.4% 0.0% 24.7% | |TERMINAL (d) | 1/33 (3%) 1/22 (5%) 0/28 (0%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 647 561 --- 516 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.669 P=0.742 P=0.719 P=0.526N P<0.001 ** | |POLY 3 | P=0.004 ** P=0.745 P=0.756 P=0.753 P=0.504N P=0.015 * | |POLY 1.5 | P=0.004 ** P=0.752 P=0.759 P=0.755 P=0.501N P=0.037 * | |POLY 6 | P=0.022 * P=0.731 P=0.750 P=0.747 P=0.511N P=0.005 ** | |LOGISTIC REGRESSION| P=0.021 * P=0.669 P=0.761 P=0.753N (e) P=0.027 * | |COCH-ARM / FISHERS | P=0.007 ** P=0.753N P=0.753N P=0.753N P=0.500N P=0.102 | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 2/50 (4%) 0/50 (0%) 5/50 (10%) 1/50 (2%) | |POLY-3 RATE (b) | 2/43.56 1/39.94 2/42.07 0/40.79 5/42.80 1/17.83 | |POLY-3 PERCENT (g) | 4.6% 2.5% 4.8% 0.0% 11.7% 5.6% | |TERMINAL (d) | 0/33 (0%) 1/22 (5%) 1/28 (4%) 0/22 (0%) 2/29 (7%) 0/0 (0%) | |FIRST INCIDENCE | 611 729 (T) 591 --- 630 668 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004 ** P=0.581N P=0.661 P=0.246N P=0.197 P=0.159 | |POLY 3 | P=0.123 P=0.530N P=0.682 P=0.252N P=0.208 P=0.657 | |POLY 1.5 | P=0.302 P=0.516N P=0.689 P=0.246N P=0.214 P=0.650N | |POLY 6 | P=0.039 * P=0.555N P=0.668 P=0.263N P=0.196 P=0.490 | |LOGISTIC REGRESSION| P=0.370 P=0.493N P=0.694N P=0.217N P=0.216 P=0.844 | |COCH-ARM / FISHERS | P=0.605 P=0.500N P=0.691N P=0.247N P=0.218 P=0.500N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 45/50 (90%) 46/50 (92%) 44/50 (88%) 42/50 (84%) 40/50 (80%) 20/50 (40%) | |POLY-3 RATE (b) | 45/48.80 46/47.73 44/48.32 42/46.37 40/46.94 20/30.51 | |POLY-3 PERCENT (g) | 92.2% 96.4% 91.1% 90.6% 85.2% 65.6% | |TERMINAL (d) | 31/33 (94%) 22/22 (100%) 26/28 (93%) 22/22 (100%) 26/29 (90%) 0/0 (0%) | |FIRST INCIDENCE | 437 407 444 252 451 407 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.020 * P=0.284 P=0.083 P=0.512N P<0.001 ** | |POLY 3 | P<0.001N** P=0.312 P=0.568N P=0.536N P=0.205N P<0.001N** | |POLY 1.5 | P<0.001N** P=0.387 P=0.534N P=0.411N P=0.159N P<0.001N** | |POLY 6 | P=0.010N* P=0.227 P=0.613N P=0.639 P=0.298N P=0.102N | |LOGISTIC REGRESSION| P<0.001N** P=0.426 P=0.504N P=0.358N P=0.116N P=0.002N** | |COCH-ARM / FISHERS | P<0.001N** P=0.500 P=0.500N P=0.277N P=0.131N P<0.001N** | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/50 (18%) 8/50 (16%) 9/50 (18%) 13/50 (26%) 22/50 (44%) 2/50 (4%) | |POLY-3 RATE (b) | 9/43.47 8/40.81 9/42.52 13/41.33 22/43.03 2/19.24 | |POLY-3 PERCENT (g) | 20.7% 19.6% 21.2% 31.5% 51.1% 10.4% | |TERMINAL (d) | 7/33 (21%) 6/22 (27%) 7/28 (25%) 10/22 (46%) 19/29 (66%) 0/0 (0%) | |FIRST INCIDENCE | 640 600 572 646 576 393 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.413 P=0.477 P=0.051 P<0.001 ** P=0.281 | |POLY 3 | P=0.103 P=0.558N P=0.584 P=0.187 P=0.002 ** P=0.291N | |POLY 1.5 | P=0.488N P=0.530N P=0.596 P=0.203 P=0.003 ** P=0.113N | |POLY 6 | P<0.001 ** P=0.608N P=0.557 P=0.159 P<0.001 ** P=0.609N | |LOGISTIC REGRESSION| P=0.074 P=0.586N P=0.570 P=0.153 P=0.002 ** P=0.208N | |COCH-ARM / FISHERS | P=0.047N* P=0.500N P=0.602N P=0.235 P=0.004 ** P=0.026N* | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 6/50 (12%) 4/50 (8%) 12/50 (24%) 13/50 (26%) | |POLY-3 RATE (b) | 1/42.87 2/39.94 6/42.86 4/41.06 12/42.82 13/25.89 | |POLY-3 PERCENT (g) | 2.3% 5.0% 14.0% 9.7% 28.0% 50.2% | |TERMINAL (d) | 1/33 (3%) 2/22 (9%) 3/28 (11%) 2/22 (9%) 9/29 (31%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 571 678 587 393 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.359 P=0.046 * P=0.099 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.475 P=0.055 P=0.165 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.487 P=0.056 P=0.169 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.455 P=0.052 P=0.156 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.359 P=0.059 P=0.146 P<0.001 ** P=0.013 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.500 P=0.056 P=0.181 P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 4/50 (8%) 0/50 (0%) 1/50 (2%) 3/50 (6%) | |POLY-3 RATE (b) | 2/43.66 1/40.77 4/42.65 0/40.79 1/41.99 3/19.82 | |POLY-3 PERCENT (g) | 4.6% 2.5% 9.4% 0.0% 2.4% 15.1% | |TERMINAL (d) | 1/33 (3%) 0/22 (0%) 1/28 (4%) 0/22 (0%) 1/29 (3%) 0/0 (0%) | |FIRST INCIDENCE | 437 407 591 --- 729 (T) 447 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.042 * P=0.549N P=0.311 P=0.289N P=0.528N P=0.219 | |POLY 3 | P=0.217 P=0.524N P=0.326 P=0.252N P=0.514N P=0.205 | |POLY 1.5 | P=0.247 P=0.512N P=0.332 P=0.247N P=0.506N P=0.322 | |POLY 6 | P=0.327 P=0.544N P=0.317 P=0.261N P=0.527N P=0.108 | |LOGISTIC REGRESSION| P=0.439N P=0.434N P=0.334 P=0.187N P=0.515N P=0.433N | |COCH-ARM / FISHERS | P=0.353 P=0.500N P=0.339 P=0.247N P=0.500N P=0.500 | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) 1/50 (2%) 7/50 (14%) | |POLY-3 RATE (b) | 0/42.87 0/39.94 2/42.28 0/40.79 1/42.62 7/22.18 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.7% 0.0% 2.4% 31.6% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 617 --- 524 393 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) P=0.226 (e) P=0.513 P<0.001 ** | |POLY 3 | P<0.001 ** (e) P=0.234 (e) P=0.499 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) P=0.236 (e) P=0.500 P<0.001 ** | |POLY 6 | P<0.001 ** (e) P=0.229 (e) P=0.494 P<0.001 ** | |LOGISTIC REGRESSION| P=0.010 * (e) P=0.236 (e) P=0.416 P=0.075 | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.247 (e) P=0.500 P=0.006 ** | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 13/50 (26%) 8/50 (16%) 9/50 (18%) 6/50 (12%) 4/50 (8%) 5/50 (10%) | |POLY-3 RATE (b) | 13/44.34 8/41.50 9/43.56 6/41.12 4/42.44 5/21.21 | |POLY-3 PERCENT (g) | 29.3% 19.3% 20.7% 14.6% 9.4% 23.6% | |TERMINAL (d) | 9/33 (27%) 4/22 (18%) 6/28 (21%) 4/22 (18%) 2/29 (7%) 0/0 (0%) | |FIRST INCIDENCE | 468 573 444 660 657 352 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.083 P=0.406N P=0.344N P=0.217N P=0.034N* P=0.046 * | |POLY 3 | P=0.231N P=0.201N P=0.244N P=0.082N P=0.017N* P=0.431N | |POLY 1.5 | P=0.162N P=0.183N P=0.235N P=0.074N P=0.015N* P=0.170N | |POLY 6 | P=0.245N P=0.237N P=0.269N P=0.098N P=0.021N* P=0.388 | |LOGISTIC REGRESSION| P=0.095N P=0.179N P=0.233N P=0.075N P=0.017N* P=0.117N | |COCH-ARM / FISHERS | P=0.060N P=0.163N P=0.235N P=0.062N P=0.016N* P=0.033N* | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/50 (18%) 7/50 (14%) 9/50 (18%) 8/50 (16%) 15/50 (30%) 3/50 (6%) | |POLY-3 RATE (b) | 9/42.91 7/41.10 9/42.34 8/43.14 15/42.64 3/19.63 | |POLY-3 PERCENT (g) | 21.0% 17.0% 21.3% 18.5% 35.2% 15.3% | |TERMINAL (d) | 8/33 (24%) 3/22 (14%) 6/28 (21%) 4/22 (18%) 13/29 (45%) 0/0 (0%) | |FIRST INCIDENCE | 720 520 647 252 570 393 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** P=0.533 P=0.468 P=0.429 P=0.058 P=0.023 * | |POLY 3 | P=0.247 P=0.428N P=0.592 P=0.495N P=0.107 P=0.435N | |POLY 1.5 | P=0.465N P=0.410N P=0.600 P=0.494N P=0.115 P=0.209N | |POLY 6 | P=0.039 * P=0.461N P=0.576 P=0.511N P=0.090 P=0.473 | |LOGISTIC REGRESSION| P=0.571N P=0.482N P=0.529 P=0.490N P=0.066 P=0.714 | |COCH-ARM / FISHERS | P=0.092N P=0.393N P=0.602N P=0.500N P=0.121 P=0.061N | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/50 (16%) 10/50 (20%) 10/50 (20%) 11/50 (22%) 23/50 (46%) 5/50 (10%) | |POLY-3 RATE (b) | 8/43.21 10/40.68 10/43.30 11/41.98 23/43.73 5/20.88 | |POLY-3 PERCENT (g) | 18.5% 24.6% 23.1% 26.2% 52.6% 24.0% | |TERMINAL (d) | 7/33 (21%) 8/22 (36%) 5/28 (18%) 4/22 (18%) 18/29 (62%) 0/0 (0%) | |FIRST INCIDENCE | 636 613 444 646 570 407 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.133 P=0.292 P=0.120 P<0.001 ** P=0.004 ** | |POLY 3 | P=0.029 * P=0.340 P=0.397 P=0.276 P<0.001 ** P=0.437 | |POLY 1.5 | P=0.282 P=0.367 P=0.402 P=0.284 P<0.001 ** P=0.557N | |POLY 6 | P<0.001 ** P=0.295 P=0.383 P=0.263 P<0.001 ** P=0.180 | |LOGISTIC REGRESSION| P=0.046 * P=0.273 P=0.383 P=0.250 P<0.001 ** P=0.592 | |COCH-ARM / FISHERS | P=0.219N P=0.398 P=0.398 P=0.306 P<0.001 ** P=0.277N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 3/50 (6%) 4/50 (8%) 4/50 (8%) 15/50 (30%) | |POLY-3 RATE (b) | 4/44.16 2/40.27 3/42.40 4/41.32 4/43.17 15/27.82 | |POLY-3 PERCENT (g) | 9.1% 5.0% 7.1% 9.7% 9.3% 53.9% | |TERMINAL (d) | 0/33 (0%) 1/22 (5%) 1/28 (4%) 0/22 (0%) 1/29 (3%) 0/0 (0%) | |FIRST INCIDENCE | 545 638 572 638 524 393 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.426N P=0.544N P=0.556 P=0.601 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.380N P=0.522N P=0.607 P=0.631 P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.360N P=0.510N P=0.620 P=0.639 P<0.001 ** | |POLY 6 | P<0.001 ** P=0.415N P=0.544N P=0.584 P=0.613 P<0.001 ** | |LOGISTIC REGRESSION| P=0.005 ** P=0.316N P=0.498N P=0.635N P=0.631 P=0.283 | |COCH-ARM / FISHERS | P<0.001 ** P=0.339N P=0.500N P=0.643N P=0.643N P=0.005 ** | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 4/50 (8%) 4/50 (8%) 3/50 (6%) 10/50 (20%) | |POLY-3 RATE (b) | 2/42.87 1/40.16 4/43.05 4/41.72 3/42.74 10/23.86 | |POLY-3 PERCENT (g) | 4.7% 2.5% 9.3% 9.6% 7.0% 41.9% | |TERMINAL (d) | 2/33 (6%) 0/22 (0%) 1/28 (4%) 1/22 (5%) 1/29 (3%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 672 444 561 524 400 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.616N P=0.299 P=0.241 P=0.457 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.523N P=0.338 P=0.324 P=0.499 P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.512N P=0.341 P=0.327 P=0.502 P=0.002 ** | |POLY 6 | P<0.001 ** P=0.541N P=0.330 P=0.315 P=0.489 P<0.001 ** | |LOGISTIC REGRESSION| P=0.026 * P=0.545N P=0.338 P=0.329 P=0.500 P=0.045 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.500N P=0.339 P=0.339 P=0.500 P=0.014 * | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Hepatocyte | | Cytomegaly | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 7/50 (14%) 23/50 (46%) 32/50 (64%) 29/50 (58%) | |POLY-3 RATE (b) | 0/42.87 0/39.94 7/42.54 23/42.07 32/45.36 29/36.57 | |POLY-3 PERCENT (g) | 0.0% 0.0% 16.5% 54.7% 70.5% 79.3% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 4/28 (14%) 16/22 (73%) 24/29 (83%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 572 650 451 350 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) P=0.007 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) P=0.007 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) P=0.007 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) P=0.006 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) P=0.009 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.006 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hyperplasia Regenerative | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 8/50 (16%) 50/50 (100%) | |POLY-3 RATE (b) | 0/42.87 0/39.94 0/41.60 0/40.79 8/42.53 50/50.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 18.8% 100.0% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 6/29 (21%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- 656 350 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) P=0.003 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) (e) P=0.003 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) (e) P=0.004 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) (e) P=0.003 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) P=0.004 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P=0.003 ** P<0.001 ** | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Hepatocyte | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 5/50 (10%) 7/50 (14%) 4/50 (8%) 3/50 (6%) 5/50 (10%) | |POLY-3 RATE (b) | 4/43.89 5/41.01 7/43.76 4/41.57 3/42.62 5/20.97 | |POLY-3 PERCENT (g) | 9.1% 12.2% 16.0% 9.6% 7.0% 23.9% | |TERMINAL (d) | 1/33 (3%) 1/22 (5%) 2/28 (7%) 0/22 (0%) 2/29 (7%) 0/0 (0%) | |FIRST INCIDENCE | 393 573 437 651 524 460 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.006 ** P=0.361 P=0.228 P=0.527 P=0.550N P=0.031 * | |POLY 3 | P=0.299 P=0.457 P=0.258 P=0.614 P=0.516N P=0.137 | |POLY 1.5 | P=0.401 P=0.476 P=0.261 P=0.622 P=0.507N P=0.269 | |POLY 6 | P=0.310 P=0.428 P=0.249 P=0.600 P=0.535N P=0.049 * | |LOGISTIC REGRESSION| P=0.274N P=0.525 P=0.258 P=0.626N P=0.510N P=0.529N | |COCH-ARM / FISHERS | P=0.529N P=0.500 P=0.262 P=0.643N P=0.500N P=0.500 | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Liver: Kupffer Cell | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 3/50 (6%) 2/50 (4%) 6/50 (12%) 4/50 (8%) | |POLY-3 RATE (b) | 0/42.87 2/40.76 3/42.41 2/42.26 6/44.30 4/20.52 | |POLY-3 PERCENT (g) | 0.0% 4.9% 7.1% 4.7% 13.5% 19.5% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 1/29 (3%) 0/0 (0%) | |FIRST INCIDENCE | --- 573 562 307 463 459 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.221 P=0.113 P=0.238 P=0.018 * P=0.031 * | |POLY 3 | P=0.005 ** P=0.226 P=0.116 P=0.234 P=0.017 * P=0.013 * | |POLY 1.5 | P=0.022 * P=0.231 P=0.118 P=0.235 P=0.017 * P=0.026 * | |POLY 6 | P=0.002 ** P=0.216 P=0.112 P=0.229 P=0.016 * P=0.006 ** | |LOGISTIC REGRESSION| P=0.543N P=0.258 P=0.121 P=0.396 P=0.011 * P=0.359 | |COCH-ARM / FISHERS | P=0.104 P=0.247 P=0.121 P=0.247 P=0.013 * P=0.059 | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 7/50 (14%) 2/50 (4%) 8/50 (16%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 4/44.42 7/42.43 2/42.54 8/42.96 1/41.99 1/18.32 | |POLY-3 PERCENT (g) | 9.0% 16.5% 4.7% 18.6% 2.4% 5.5% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 1/29 (3%) 0/0 (0%) | |FIRST INCIDENCE | 468 519 444 293 729 (T) 478 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.373N P=0.209 P=0.370N P=0.144 P=0.203N P=0.705 | |POLY 3 | P=0.125N P=0.234 P=0.357N P=0.159 P=0.196N P=0.514N | |POLY 1.5 | P=0.082N P=0.247 P=0.346N P=0.166 P=0.187N P=0.346N | |POLY 6 | P=0.160N P=0.212 P=0.378N P=0.147 P=0.213N P=0.597 | |LOGISTIC REGRESSION| P=0.003N** P=0.310 P=0.348N P=0.218 P=0.187N P=0.058N | |COCH-ARM / FISHERS | P=0.032N* P=0.262 P=0.339N P=0.178 P=0.181N P=0.181N | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 0/42.87 0/39.94 0/41.60 0/40.79 1/42.62 2/19.23 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 2.4% 10.4% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- 524 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.009 ** (e) (e) (e) P=0.513 P=0.221 | |POLY 3 | P=0.005 ** (e) (e) (e) P=0.499 P=0.115 | |POLY 1.5 | P=0.008 ** (e) (e) (e) P=0.500 P=0.160 | |POLY 6 | P=0.014 * (e) (e) (e) P=0.494 P=0.080 | |LOGISTIC REGRESSION| P=0.214 (e) (e) (e) P=0.416 P=0.706 | |COCH-ARM / FISHERS | P=0.020 * (e) (e) (e) P=0.500 P=0.247 | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 7/50 (14%) 1/50 (2%) 3/50 (6%) 5/50 (10%) 19/50 (38%) | |POLY-3 RATE (b) | 4/44.66 7/42.41 1/41.87 3/41.59 5/43.43 19/29.60 | |POLY-3 PERCENT (g) | 9.0% 16.5% 2.4% 7.2% 11.5% 64.2% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 1/29 (3%) 0/0 (0%) | |FIRST INCIDENCE | 468 573 658 642 524 350 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.229 P=0.204N P=0.514N P=0.479 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.231 P=0.198N P=0.539N P=0.482 P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.244 P=0.189N P=0.525N P=0.493 P<0.001 ** | |POLY 6 | P<0.001 ** P=0.211 P=0.215N P=0.561N P=0.462 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.310 P=0.182N P=0.441N P=0.469 P=0.046 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.262 P=0.181N P=0.500N P=0.500 P<0.001 ** | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 45/50 (90%) 41/50 (82%) 47/50 (94%) 44/50 (88%) 49/50 (98%) 42/50 (84%) | |POLY-3 RATE (b) | 45/48.81 41/46.78 47/48.64 44/45.77 49/49.65 42/44.19 | |POLY-3 PERCENT (g) | 92.2% 87.7% 96.6% 96.1% 98.7% 95.0% | |TERMINAL (d) | 32/33 (97%) 22/22 (100%) 28/28 (100%) 22/22 (100%) 29/29 (100%) 0/0 (0%) | |FIRST INCIDENCE | 393 407 437 552 451 350 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.094 P=0.123 P=0.037 * P=0.099 P<0.001 ** | |POLY 3 | P=0.245 P=0.329N P=0.277 P=0.332 P=0.112 P=0.434 | |POLY 1.5 | P=0.496 P=0.276N P=0.311 P=0.449 P=0.106 P=0.654N | |POLY 6 | P=0.094 P=0.386N P=0.243 P=0.284 P=0.133 P=0.236 | |LOGISTIC REGRESSION| P=0.027 * P=0.234N P=0.353 P=0.625 P=0.104 P=0.498 | |COCH-ARM / FISHERS | P=0.313N P=0.194N P=0.357 P=0.500N P=0.102 P=0.277N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung | | Metaplasia Osseous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/42.87 2/40.70 0/41.60 0/40.79 0/41.99 0/17.60 | |POLY-3 PERCENT (g) | 0.0% 4.9% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 520 --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.608N P=0.214 (e) (e) (e) (e) | |POLY 3 | P=0.337N P=0.225 (e) (e) (e) (e) | |POLY 1.5 | P=0.369N P=0.231 (e) (e) (e) (e) | |POLY 6 | P=0.376N P=0.215 (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.293N P=0.258 (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.393N P=0.247 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/50 (10%) 4/50 (8%) 10/50 (20%) 5/50 (10%) 5/50 (10%) 7/50 (14%) | |POLY-3 RATE (b) | 5/42.87 4/40.29 10/42.37 5/40.79 5/41.99 7/21.20 | |POLY-3 PERCENT (g) | 11.7% 9.9% 23.6% 12.3% 11.9% 33.0% | |TERMINAL (d) | 5/33 (15%) 3/22 (14%) 8/28 (29%) 5/22 (23%) 5/29 (17%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 631 591 729 (T) 729 (T) 459 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.554 P=0.074 P=0.362 P=0.548 P<0.001 ** | |POLY 3 | P=0.114 P=0.539N P=0.120 P=0.599 P=0.618 P=0.057 | |POLY 1.5 | P=0.200 P=0.520N P=0.126 P=0.610 P=0.627 P=0.154 | |POLY 6 | P=0.095 P=0.571N P=0.110 P=0.578 P=0.598 P=0.013 * | |LOGISTIC REGRESSION| P=0.004 ** P=0.619N P=0.098 P=0.362 P=0.548 P=0.017 * | |COCH-ARM / FISHERS | P=0.431 P=0.500N P=0.131 P=0.630N P=0.630N P=0.380 | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/49 (0%) 0/48 (0%) 3/50 (6%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/42.87 0/39.58 0/40.38 3/41.07 0/41.99 0/17.60 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 7.3% 0.0% 0.0% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/27 (0%) 2/22 (9%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- 651 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.919N (e) (e) P=0.078 (e) (e) | |POLY 3 | P=0.543N (e) (e) P=0.111 (e) (e) | |POLY 1.5 | P=0.492N (e) (e) P=0.113 (e) (e) | |POLY 6 | P=0.686N (e) (e) P=0.106 (e) (e) | |LOGISTIC REGRESSION| P=0.763N (e) (e) P=0.110 (e) (e) | |COCH-ARM / FISHERS | P=0.430N (e) (e) P=0.121 (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 3/49 (6%) 1/48 (2%) 5/50 (10%) 5/50 (10%) 0/50 (0%) | |POLY-3 RATE (b) | 2/42.87 3/39.89 1/40.38 5/40.89 5/42.27 0/17.60 | |POLY-3 PERCENT (g) | 4.7% 7.5% 2.5% 12.2% 11.8% 0.0% | |TERMINAL (d) | 2/33 (6%) 2/22 (9%) 1/27 (4%) 3/22 (14%) 4/29 (14%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 644 729 (T) 715 654 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.268 P=0.343 P=0.570N P=0.094 P=0.174 P=1.000N | |POLY 3 | P=0.460 P=0.467 P=0.521N P=0.196 P=0.209 P=0.457N | |POLY 1.5 | P=0.401N P=0.479 P=0.516N P=0.203 P=0.215 P=0.349N | |POLY 6 | P=0.179 P=0.446 P=0.532N P=0.183 P=0.197 P=0.589N | |LOGISTIC REGRESSION| P=0.382 P=0.435 P=0.570N P=0.124 P=0.183 (e) | |COCH-ARM / FISHERS | P=0.154N P=0.490 P=0.515N P=0.218 P=0.218 P=0.247N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 24 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/50 (10%) 2/49 (4%) 2/48 (4%) 11/50 (22%) 3/50 (6%) 0/50 (0%) | |POLY-3 RATE (b) | 5/42.87 2/39.77 2/40.44 11/41.92 3/42.48 0/17.60 | |POLY-3 PERCENT (g) | 11.7% 5.0% 5.0% 26.2% 7.1% 0.0% | |TERMINAL (d) | 5/33 (15%) 1/22 (5%) 1/27 (4%) 5/22 (23%) 2/29 (7%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 679 715 638 581 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.652N P=0.391N P=0.299N P=0.023 * P=0.418N P=1.000N | |POLY 3 | P=0.221N P=0.246N P=0.239N P=0.072 P=0.361N P=0.203N | |POLY 1.5 | P=0.100N P=0.236N P=0.234N P=0.075 P=0.356N P=0.093N | |POLY 6 | P=0.441N P=0.267N P=0.252N P=0.067 P=0.374N P=0.416N | |LOGISTIC REGRESSION| P=0.320N P=0.312N P=0.290N P=0.060 P=0.380N (e) | |COCH-ARM / FISHERS | P=0.026N* P=0.226N P=0.235N P=0.086 P=0.357N P=0.028N* | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 3/50 (6%) 3/50 (6%) 3/50 (6%) 1/50 (2%) 9/50 (18%) | |POLY-3 RATE (b) | 4/42.87 3/40.88 3/42.54 3/41.79 1/42.15 9/23.79 | |POLY-3 PERCENT (g) | 9.3% 7.3% 7.1% 7.2% 2.4% 37.8% | |TERMINAL (d) | 4/33 (12%) 0/22 (0%) 1/28 (4%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 636 444 552 686 393 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.650N P=0.571N P=0.641N P=0.221N P<0.001 ** | |POLY 3 | P=0.003 ** P=0.526N P=0.504N P=0.514N P=0.183N P=0.008 ** | |POLY 1.5 | P=0.004 ** P=0.514N P=0.500N P=0.511N P=0.180N P=0.030 * | |POLY 6 | P=0.005 ** P=0.547N P=0.517N P=0.524N P=0.191N P<0.001 ** | |LOGISTIC REGRESSION| P=0.140 P=0.526N P=0.501N P=0.511N P=0.206N P=0.248 | |COCH-ARM / FISHERS | P=0.011 * P=0.500N P=0.500N P=0.500N P=0.181N P=0.117 | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 25 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/50 (10%) 8/50 (16%) 9/50 (18%) 5/50 (10%) 7/50 (14%) 25/50 (50%) | |POLY-3 RATE (b) | 5/44.55 8/40.81 9/42.41 5/40.87 7/42.46 25/32.79 | |POLY-3 PERCENT (g) | 11.2% 19.6% 21.2% 12.2% 16.5% 76.3% | |TERMINAL (d) | 1/33 (3%) 5/22 (23%) 6/28 (21%) 4/22 (18%) 6/29 (21%) 0/0 (0%) | |FIRST INCIDENCE | 483 613 591 707 590 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.153 P=0.147 P=0.478 P=0.320 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.219 P=0.163 P=0.575 P=0.345 P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.244 P=0.178 P=0.596 P=0.363 P<0.001 ** | |POLY 6 | P<0.001 ** P=0.182 P=0.141 P=0.540 P=0.311 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.280 P=0.195 P=0.630 P=0.380 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.277 P=0.194 P=0.630N P=0.380 P<0.001 ** | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 23/50 (46%) 22/50 (44%) 32/50 (64%) 15/50 (30%) 16/50 (32%) 31/50 (62%) | |POLY-3 RATE (b) | 23/47.15 22/43.02 32/45.35 15/42.50 16/44.30 31/37.24 | |POLY-3 PERCENT (g) | 48.8% 51.1% 70.6% 35.3% 36.1% 83.3% | |TERMINAL (d) | 12/33 (36%) 12/22 (55%) 22/28 (79%) 8/22 (36%) 9/29 (31%) 0/0 (0%) | |FIRST INCIDENCE | 393 573 444 552 570 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.230 P=0.029 * P=0.363N P=0.236N P<0.001 ** | |POLY 3 | P=0.003 ** P=0.495 P=0.022 * P=0.137N P=0.152N P<0.001 ** | |POLY 1.5 | P=0.012 * P=0.562 P=0.033 * P=0.112N P=0.131N P=0.005 ** | |POLY 6 | P<0.001 ** P=0.407 P=0.012 * P=0.181N P=0.190N P<0.001 ** | |LOGISTIC REGRESSION| P=0.026 * P=0.515N P=0.053 P=0.078N P=0.108N P=0.300 | |COCH-ARM / FISHERS | P=0.067 P=0.500N P=0.054 P=0.074N P=0.109N P=0.080 | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 26 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 3/50 (6%) 4/47 (9%) 0/49 (0%) 6/49 (12%) | |POLY-3 RATE (b) | 1/43.28 2/40.35 3/42.35 4/40.25 0/40.99 6/21.44 | |POLY-3 PERCENT (g) | 2.3% 5.0% 7.1% 9.9% 0.0% 28.0% | |TERMINAL (d) | 0/33 (0%) 1/22 (5%) 1/28 (4%) 2/22 (9%) 0/28 (0%) 0/0 (0%) | |FIRST INCIDENCE | 611 613 591 618 --- 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.440 P=0.279 P=0.138 P=0.514N P=0.002 ** | |POLY 3 | P=0.021 * P=0.475 P=0.297 P=0.156 P=0.511N P=0.006 ** | |POLY 1.5 | P=0.025 * P=0.487 P=0.302 P=0.158 P=0.507N P=0.016 * | |POLY 6 | P=0.041 * P=0.455 P=0.287 P=0.151 P=0.519N P<0.001 ** | |LOGISTIC REGRESSION| P=0.237 P=0.515 P=0.306 P=0.163 P=0.520N P=0.319 | |COCH-ARM / FISHERS | P=0.050 P=0.500 P=0.309 P=0.162 P=0.505N P=0.053 | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 1/50 (2%) 2/50 (4%) 2/47 (4%) 3/49 (6%) 2/49 (4%) | |POLY-3 RATE (b) | 3/43.28 1/39.94 2/41.60 2/39.99 3/40.99 2/18.48 | |POLY-3 PERCENT (g) | 6.9% 2.5% 4.8% 5.0% 7.3% 10.8% | |TERMINAL (d) | 2/33 (6%) 1/22 (5%) 2/28 (7%) 1/22 (5%) 3/28 (11%) 0/0 (0%) | |FIRST INCIDENCE | 611 729 (T) 729 (T) 618 729 (T) 447 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** P=0.426N P=0.566N P=0.604N P=0.592 P=0.059 | |POLY 3 | P=0.233 P=0.334N P=0.518N P=0.536N P=0.638 P=0.499 | |POLY 1.5 | P=0.358 P=0.320N P=0.508N P=0.533N P=0.647 P=0.658 | |POLY 6 | P=0.194 P=0.359N P=0.536N P=0.546N P=0.618 P=0.310 | |LOGISTIC REGRESSION| P=0.193 P=0.330N P=0.518N P=0.529N P=0.632 P=0.694 | |COCH-ARM / FISHERS | P=0.577 P=0.309N P=0.500N P=0.530N P=0.651 P=0.510N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 27 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Pancreatic | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/26 (0%) 0/24 (0%) 0/36 (0%) 0/19 (0%) 0/21 (0%) 2/40 (5%) | |POLY-3 RATE (b) | 0/21.36 0/20.27 0/31.39 0/16.17 0/17.48 2/16.18 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 12.4% | |TERMINAL (d) | 0/14 (0%) 0/13 (0%) 0/23 (0%) 0/9 (0%) 0/12 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- --- 352 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.005 ** (e) (e) (e) (e) P=0.189 | |POLY 3 | P=0.014 * (e) (e) (e) (e) P=0.182 | |POLY 1.5 | P=0.019 * (e) (e) (e) (e) P=0.248 | |POLY 6 | P=0.043 * (e) (e) (e) (e) P=0.118 | |LOGISTIC REGRESSION| P=0.435 (e) (e) (e) (e) P=0.664 | |COCH-ARM / FISHERS | P=0.032 * (e) (e) (e) (e) P=0.364 | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Pancreatic | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/26 (0%) 1/24 (4%) 2/36 (6%) 0/19 (0%) 4/21 (19%) 1/40 (3%) | |POLY-3 RATE (b) | 0/21.36 1/20.27 2/31.87 0/16.17 4/17.65 1/15.29 | |POLY-3 PERCENT (g) | 0.0% 4.9% 6.3% 0.0% 22.7% 6.5% | |TERMINAL (d) | 0/14 (0%) 1/13 (8%) 0/23 (0%) 0/9 (0%) 3/12 (25%) 0/0 (0%) | |FIRST INCIDENCE | --- 729 (T) 654 --- 686 472 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** P=0.485 P=0.219 (e) P=0.044 * P=0.410 | |POLY 3 | P=0.116 P=0.490 P=0.330 (e) P=0.030 * P=0.436 | |POLY 1.5 | P=0.321 P=0.489 P=0.323 (e) P=0.031 * P=0.508 | |POLY 6 | P=0.017 * P=0.486 P=0.338 (e) P=0.029 * P=0.345 | |LOGISTIC REGRESSION| P=0.296 P=0.485 P=0.297 (e) P=0.033 * P=0.819 | |COCH-ARM / FISHERS | P=0.609N P=0.480 P=0.333 (e) P=0.034 * P=0.606 | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 28 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Lymph Node: Renal | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/26 (0%) 0/24 (0%) 2/36 (6%) 0/19 (0%) 2/21 (10%) 1/40 (3%) | |POLY-3 RATE (b) | 0/21.36 0/20.27 2/31.44 0/16.17 2/18.13 1/15.39 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.4% 0.0% 11.0% 6.5% | |TERMINAL (d) | 0/14 (0%) 0/13 (0%) 1/23 (4%) 0/9 (0%) 0/12 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 715 --- 587 407 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.046 * (e) P=0.278 (e) P=0.227 P=0.483 | |POLY 3 | P=0.180 (e) P=0.326 (e) P=0.196 P=0.438 | |POLY 1.5 | P=0.334 (e) P=0.321 (e) P=0.193 P=0.509 | |POLY 6 | P=0.090 (e) P=0.332 (e) P=0.199 P=0.346 | |LOGISTIC REGRESSION| P=0.679 (e) P=0.334 (e) P=0.175 P=0.851 | |COCH-ARM / FISHERS | P=0.555 (e) P=0.333 (e) P=0.194 P=0.606 | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 48/50 (96%) 46/50 (92%) 46/50 (92%) 45/50 (90%) 44/49 (90%) 43/49 (88%) | |POLY-3 RATE (b) | 48/49.22 46/47.77 46/48.31 45/46.59 44/48.22 43/44.25 | |POLY-3 PERCENT (g) | 97.5% 96.3% 95.2% 96.6% 91.2% 97.2% | |TERMINAL (d) | 33/33 (100%) 22/22 (100%) 27/28 (96%) 22/22 (100%) 26/29 (90%) 0/0 (0%) | |FIRST INCIDENCE | 393 407 437 451 451 350 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.046 * P=0.320 P=0.077 P=0.535 P<0.001 ** | |POLY 3 | P=0.612N P=0.613N P=0.468N P=0.654N P=0.165N P=0.771N | |POLY 1.5 | P=0.398N P=0.483N P=0.400N P=0.502N P=0.176N P=0.405N | |POLY 6 | P=0.522 P=0.804N P=0.573N P=0.786N P=0.169N P=0.686 | |LOGISTIC REGRESSION| P=0.082 P=0.394N P=0.311N P=0.361N P=0.203N P=0.494 | |COCH-ARM / FISHERS | P=0.165N P=0.339N P=0.339N P=0.218N P=0.210N P=0.128N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 29 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Mesentery | | Accessory Spleen | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/10 (20%) 0/10 (0%) 1/18 (6%) 2/14 (14%) 1/13 (8%) 0/5 (0%) | |POLY-3 RATE (b) | 2/9.48 0/8.66 1/15.81 2/12.97 1/9.97 0/2.17 | |POLY-3 PERCENT (g) | 21.1% 0.0% 6.3% 15.4% 10.0% 0.0% | |TERMINAL (d) | 2/7 (29%) 0/6 (0%) 1/11 (9%) 1/8 (13%) 1/5 (20%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) --- 729 (T) 638 729 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.838 P=0.265N P=0.337N P=0.659N P=0.627N P=1.000N | |POLY 3 | P=0.530N P=0.246N P=0.317N P=0.581N P=0.482N P=0.576N | |POLY 1.5 | P=0.503N P=0.237N P=0.307N P=0.575N P=0.448N P=0.497N | |POLY 6 | P=0.625 P=0.262N P=0.328N P=0.592N P=0.531N P=0.670N | |LOGISTIC REGRESSION| P=0.849N (e) P=0.337N P=0.569N P=0.627N (e) | |COCH-ARM / FISHERS | P=0.449N P=0.237N P=0.284N P=0.563N P=0.398N P=0.429N | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/10 (80%) 10/10 (100%) 18/18 (100%) 12/14 (86%) 9/13 (69%) 3/5 (60%) | |POLY-3 RATE (b) | 8/10.00 10/10.00 18/18.00 12/14.00 9/12.56 3/3.87 | |POLY-3 PERCENT (g) | 80.0% 100.0% 100.0% 85.7% 71.6% 77.6% | |TERMINAL (d) | 5/7 (71%) 6/6 (100%) 11/11 (100%) 6/8 (75%) 2/5 (40%) 0/0 (0%) | |FIRST INCIDENCE | 611 573 518 638 463 522 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.033 * P=0.194 P=0.044 * P=0.198 P=0.339 P=0.007 ** | |POLY 3 | P=0.113N P=0.227 P=0.106 P=0.571 P=0.513N P=0.727N | |POLY 1.5 | P=0.055N P=0.227 P=0.106 P=0.571 P=0.490N P=0.595N | |POLY 6 | P=0.224N P=0.227 P=0.106 P=0.571 P=0.546N P=0.659 | |LOGISTIC REGRESSION| P=0.006N** (e) (e) (e) P=0.278N P=0.780N | |COCH-ARM / FISHERS | P=0.020N* P=0.237 P=0.119 P=0.563 P=0.463N P=0.407N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 30 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Nose | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 1/49 (2%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 2/43.61 0/39.94 1/41.91 1/41.28 0/41.99 1/18.32 | |POLY-3 PERCENT (g) | 4.6% 0.0% 2.4% 2.4% 0.0% 5.5% | |TERMINAL (d) | 1/33 (3%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | 468 --- 647 307 --- 475 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.542 P=0.284N P=0.519N P=0.556N P=0.254N P=0.681 | |POLY 3 | P=0.597N P=0.257N P=0.514N P=0.519N P=0.245N P=0.664 | |POLY 1.5 | P=0.627 P=0.248N P=0.507N P=0.515N P=0.241N P=0.647N | |POLY 6 | P=0.523N P=0.272N P=0.525N P=0.530N P=0.254N P=0.501 | |LOGISTIC REGRESSION| P=0.245N P=0.211N P=0.508N P=0.348N P=0.258N P=0.295N | |COCH-ARM / FISHERS | P=0.619N P=0.247N P=0.500N P=0.508N P=0.247N P=0.500N | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Nose | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 0/50 (0%) 2/49 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 3/43.61 0/39.94 0/41.60 2/41.28 0/41.99 1/18.23 | |POLY-3 PERCENT (g) | 6.9% 0.0% 0.0% 4.9% 0.0% 5.5% | |TERMINAL (d) | 2/33 (6%) 0/22 (0%) 0/28 (0%) 1/22 (5%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | 468 --- --- 307 --- 522 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.540 P=0.173N P=0.143N P=0.616N P=0.138N P=0.648 | |POLY 3 | P=0.533N P=0.135N P=0.127N P=0.525N P=0.125N P=0.620N | |POLY 1.5 | P=0.558N P=0.127N P=0.123N P=0.519N P=0.122N P=0.477N | |POLY 6 | P=0.466N P=0.148N P=0.134N P=0.539N P=0.132N P=0.557 | |LOGISTIC REGRESSION| P=0.258N P=0.110N P=0.119N P=0.434N P=0.123N P=0.335N | |COCH-ARM / FISHERS | P=0.527N P=0.121N P=0.121N P=0.510N P=0.121N P=0.309N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 31 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Nose: Respiratory Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 0/49 (0%) 0/50 (0%) 3/50 (6%) | |POLY-3 RATE (b) | 1/42.87 0/39.94 1/41.91 0/40.35 0/41.99 3/19.52 | |POLY-3 PERCENT (g) | 2.3% 0.0% 2.4% 0.0% 0.0% 15.4% | |TERMINAL (d) | 1/33 (3%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) --- 647 --- --- 475 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.581N P=0.742 P=0.581N P=0.526N P=0.032 * | |POLY 3 | P=0.026 * P=0.514N P=0.756 P=0.512N P=0.504N P=0.110 | |POLY 1.5 | P=0.022 * P=0.507N P=0.759 P=0.510N P=0.501N P=0.180 | |POLY 6 | P=0.108 P=0.526N P=0.750 P=0.518N P=0.511N P=0.059 | |LOGISTIC REGRESSION| P=0.123 (e) P=0.761 (e) (e) P=0.381 | |COCH-ARM / FISHERS | P=0.031 * P=0.500N P=0.753N P=0.505N P=0.500N P=0.309 | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/50 (22%) 7/49 (14%) 8/50 (16%) 9/50 (18%) 6/50 (12%) 9/50 (18%) | |POLY-3 RATE (b) | 11/44.55 7/40.72 8/44.26 9/42.25 6/42.94 9/23.66 | |POLY-3 PERCENT (g) | 24.7% 17.2% 18.1% 21.3% 14.0% 38.0% | |TERMINAL (d) | 8/33 (24%) 3/21 (14%) 2/28 (7%) 4/22 (18%) 4/29 (14%) 0/0 (0%) | |FIRST INCIDENCE | 498 328 518 293 587 440 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.469N P=0.393N P=0.520 P=0.201N P=0.002 ** | |POLY 3 | P=0.179 P=0.280N P=0.308N P=0.452N P=0.158N P=0.206 | |POLY 1.5 | P=0.299 P=0.254N P=0.304N P=0.432N P=0.149N P=0.454 | |POLY 6 | P=0.131 P=0.328N P=0.318N P=0.489N P=0.177N P=0.047 * | |LOGISTIC REGRESSION| P=0.285N P=0.214N P=0.295N P=0.400N P=0.143N P=0.449N | |COCH-ARM / FISHERS | P=0.541N P=0.232N P=0.306N P=0.402N P=0.143N P=0.402N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 32 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pancreas | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/50 (20%) 3/50 (6%) 9/50 (18%) 8/46 (17%) 4/50 (8%) 4/50 (8%) | |POLY-3 RATE (b) | 10/45.06 3/40.30 9/43.27 8/40.12 4/41.99 4/20.41 | |POLY-3 PERCENT (g) | 22.2% 7.4% 20.8% 19.9% 9.5% 19.6% | |TERMINAL (d) | 6/33 (18%) 1/22 (5%) 5/28 (18%) 6/22 (27%) 4/29 (14%) 0/0 (0%) | |FIRST INCIDENCE | 393 643 437 646 729 (T) 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.078 P=0.111N P=0.591 P=0.550 P=0.114N P=0.191 | |POLY 3 | P=0.376N P=0.053N P=0.540N P=0.505N P=0.092N P=0.531N | |POLY 1.5 | P=0.261N P=0.045N* P=0.520N P=0.492N P=0.083N P=0.269N | |POLY 6 | P=0.452N P=0.070N P=0.572N P=0.533N P=0.110N P=0.359 | |LOGISTIC REGRESSION| P=0.145N P=0.033N* P=0.491N P=0.475N P=0.074N P=0.031N* | |COCH-ARM / FISHERS | P=0.101N P=0.036N* P=0.500N P=0.475N P=0.074N P=0.074N | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pancreas: Acinus | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/50 (6%) 1/50 (2%) 0/50 (0%) 0/46 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 3/42.87 1/39.94 0/41.60 0/39.53 1/41.99 0/17.60 | |POLY-3 PERCENT (g) | 7.0% 2.5% 0.0% 0.0% 2.4% 0.0% | |TERMINAL (d) | 3/33 (9%) 1/22 (5%) 0/28 (0%) 0/22 (0%) 1/29 (3%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) --- --- 729 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.755N P=0.458N P=0.151N P=0.200N P=0.352N P=1.000N | |POLY 3 | P=0.332N P=0.331N P=0.124N P=0.133N P=0.312N P=0.342N | |POLY 1.5 | P=0.296N P=0.318N P=0.121N P=0.133N P=0.307N P=0.221N | |POLY 6 | P=0.413N P=0.352N P=0.130N P=0.137N P=0.324N P=0.514N | |LOGISTIC REGRESSION| P=0.755N P=0.458N (e) (e) P=0.352N (e) | |COCH-ARM / FISHERS | P=0.239N P=0.309N P=0.121N P=0.137N P=0.309N P=0.121N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 33 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/50 (12%) 6/48 (13%) 8/50 (16%) 8/49 (16%) 9/50 (18%) 7/49 (14%) | |POLY-3 RATE (b) | 6/43.61 6/39.53 8/42.78 8/41.54 9/43.64 7/21.98 | |POLY-3 PERCENT (g) | 13.8% 15.2% 18.7% 19.3% 20.6% 31.9% | |TERMINAL (d) | 5/33 (15%) 1/21 (5%) 6/28 (21%) 4/22 (18%) 5/29 (17%) 0/0 (0%) | |FIRST INCIDENCE | 468 605 437 638 463 400 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.405 P=0.291 P=0.214 P=0.229 P=0.003 ** | |POLY 3 | P=0.082 P=0.551 P=0.370 P=0.348 P=0.286 P=0.097 | |POLY 1.5 | P=0.200 P=0.569 P=0.381 P=0.352 P=0.290 P=0.231 | |POLY 6 | P=0.036 * P=0.525 P=0.349 P=0.339 P=0.273 P=0.024 * | |LOGISTIC REGRESSION| P=0.471 P=0.586 P=0.386 P=0.358 P=0.288 P=0.665N | |COCH-ARM / FISHERS | P=0.504 P=0.591 P=0.387 P=0.371 P=0.288 P=0.484 | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 16/50 (32%) 11/48 (23%) 19/50 (38%) 16/49 (33%) 17/50 (34%) 19/49 (39%) | |POLY-3 RATE (b) | 16/43.90 11/39.85 19/45.73 16/41.52 17/45.37 19/29.81 | |POLY-3 PERCENT (g) | 36.4% 27.6% 41.6% 38.5% 37.5% 63.7% | |TERMINAL (d) | 14/33 (42%) 5/21 (24%) 10/28 (36%) 10/22 (46%) 8/29 (28%) 0/0 (0%) | |FIRST INCIDENCE | 483 541 437 618 463 350 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.570N P=0.212 P=0.181 P=0.373 P<0.001 ** | |POLY 3 | P=0.010 * P=0.262N P=0.389 P=0.510 P=0.548 P=0.016 * | |POLY 1.5 | P=0.038 * P=0.241N P=0.373 P=0.521 P=0.532 P=0.080 | |POLY 6 | P=0.002 ** P=0.299N P=0.399 P=0.486 P=0.559 P<0.001 ** | |LOGISTIC REGRESSION| P=0.099 P=0.283N P=0.336 P=0.492 P=0.496 P=0.235 | |COCH-ARM / FISHERS | P=0.183 P=0.218N P=0.338 P=0.558 P=0.500 P=0.310 | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 34 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/50 (20%) 8/48 (17%) 9/50 (18%) 11/49 (22%) 7/50 (14%) 6/49 (12%) | |POLY-3 RATE (b) | 10/42.87 8/40.66 9/42.54 11/41.23 7/42.94 6/20.85 | |POLY-3 PERCENT (g) | 23.3% 19.7% 21.2% 26.7% 16.3% 28.8% | |TERMINAL (d) | 10/33 (30%) 1/21 (5%) 7/28 (25%) 8/22 (36%) 4/29 (14%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 513 562 638 581 469 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.512 P=0.563 P=0.176 P=0.391N P<0.001 ** | |POLY 3 | P=0.493 P=0.445N P=0.508N P=0.459 P=0.292N P=0.441 | |POLY 1.5 | P=0.408N P=0.439N P=0.501N P=0.461 P=0.291N P=0.515N | |POLY 6 | P=0.395 P=0.460N P=0.526N P=0.448 P=0.302N P=0.166 | |LOGISTIC REGRESSION| P=0.539 P=0.467N P=0.567N P=0.372 P=0.338N P=0.214 | |COCH-ARM / FISHERS | P=0.151N P=0.435N P=0.500N P=0.479 P=0.298N P=0.220N | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Salivary Glands | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/42.87 0/39.94 0/41.60 1/40.79 0/41.99 2/18.79 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.5% 0.0% 10.7% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/28 (0%) 1/22 (5%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- 729 (T) --- 527 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P=0.419 (e) P=0.076 | |POLY 3 | P=0.030 * (e) (e) P=0.490 (e) P=0.113 | |POLY 1.5 | P=0.030 * (e) (e) P=0.493 (e) P=0.158 | |POLY 6 | P=0.104 (e) (e) P=0.483 (e) P=0.079 | |LOGISTIC REGRESSION| P=0.093 (e) (e) P=0.419 (e) P=0.357 | |COCH-ARM / FISHERS | P=0.047 * (e) (e) P=0.500 (e) P=0.247 | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 35 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Skeletal Muscle | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/0 (0%) 4/6 (67%) | |POLY-3 RATE (b) | 0/0.00 0/0.88 0/0.53 0/0.68 0/0.00 4/4.68 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% 85.5% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- --- 476 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) (e) P=0.005 ** | |POLY 3 | (e) (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.057 (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.051 (e) (e) (e) (e) P=1.000 | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Skin: Subcutaneous Tissue | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/42.87 0/39.94 0/40.60 2/41.23 0/41.99 0/17.60 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.9% 0.0% 0.0% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/27 (0%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- 618 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.949N (e) (e) P=0.211 (e) (e) | |POLY 3 | P=0.591N (e) (e) P=0.228 (e) (e) | |POLY 1.5 | P=0.563N (e) (e) P=0.231 (e) (e) | |POLY 6 | P=0.724N (e) (e) P=0.223 (e) (e) | |LOGISTIC REGRESSION| P=0.629N (e) (e) P=0.239 (e) (e) | |COCH-ARM / FISHERS | P=0.534N (e) (e) P=0.247 (e) (e) | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 36 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Spleen | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) 3/50 (6%) 7/50 (14%) | |POLY-3 RATE (b) | 0/42.87 0/39.94 0/41.60 1/41.09 3/42.47 7/22.30 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.4% 7.1% 31.4% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 2/29 (7%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- 646 587 393 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P=0.505 P=0.108 P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P=0.492 P=0.116 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P=0.494 P=0.119 P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P=0.486 P=0.112 P<0.001 ** | |LOGISTIC REGRESSION| P=0.003 ** (e) (e) P=0.511 P=0.120 P=0.109 | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.500 P=0.121 P=0.006 ** | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Spleen | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 1/42.87 1/40.16 2/41.60 0/40.79 2/42.47 0/17.60 | |POLY-3 PERCENT (g) | 2.3% 2.5% 4.8% 0.0% 4.7% 0.0% | |TERMINAL (d) | 1/33 (3%) 0/22 (0%) 2/28 (7%) 0/22 (0%) 1/29 (3%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 672 729 (T) --- 587 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.721 P=0.692 P=0.442 P=0.581N P=0.470 P=1.000N | |POLY 3 | P=0.581N P=0.746 P=0.490 P=0.510N P=0.497 P=0.650N | |POLY 1.5 | P=0.457N P=0.753 P=0.496 P=0.507N P=0.500 P=0.586N | |POLY 6 | P=0.488 P=0.734 P=0.478 P=0.517N P=0.488 P=0.716N | |LOGISTIC REGRESSION| P=0.647N P=0.747 P=0.442 (e) P=0.500 (e) | |COCH-ARM / FISHERS | P=0.321N P=0.753N P=0.500 P=0.500N P=0.500 P=0.500N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 37 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 24/50 (48%) 33/50 (66%) 25/50 (50%) 26/50 (52%) 27/50 (54%) 34/50 (68%) | |POLY-3 RATE (b) | 24/46.90 33/46.20 25/46.39 26/44.48 27/44.37 34/38.85 | |POLY-3 PERCENT (g) | 51.2% 71.4% 53.9% 58.5% 60.9% 87.5% | |TERMINAL (d) | 16/33 (49%) 15/22 (68%) 14/28 (50%) 12/22 (55%) 19/29 (66%) 0/0 (0%) | |FIRST INCIDENCE | 393 328 437 307 524 350 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.006 ** P=0.322 P=0.100 P=0.203 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.031 * P=0.478 P=0.310 P=0.230 P<0.001 ** | |POLY 1.5 | P=0.005 ** P=0.038 * P=0.486 P=0.341 P=0.277 P<0.001 ** | |POLY 6 | P<0.001 ** P=0.024 * P=0.469 P=0.280 P=0.175 P<0.001 ** | |LOGISTIC REGRESSION| P=0.024 * P=0.058 P=0.515 P=0.408 P=0.339 P=0.088 | |COCH-ARM / FISHERS | P=0.057 P=0.053 P=0.500 P=0.421 P=0.345 P=0.034 * | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 37/50 (74%) 41/50 (82%) 35/50 (70%) 34/50 (68%) 35/50 (70%) 29/50 (58%) | |POLY-3 RATE (b) | 37/46.55 41/46.41 35/46.77 34/46.15 35/45.40 29/36.54 | |POLY-3 PERCENT (g) | 79.5% 88.3% 74.8% 73.7% 77.1% 79.4% | |TERMINAL (d) | 27/33 (82%) 21/22 (96%) 20/28 (71%) 16/22 (73%) 25/29 (86%) 0/0 (0%) | |FIRST INCIDENCE | 468 328 444 252 524 393 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.007 ** P=0.396 P=0.168 P=0.444 P<0.001 ** | |POLY 3 | P=0.484N P=0.171 P=0.382N P=0.332N P=0.489N P=0.615N | |POLY 1.5 | P=0.173N P=0.203 P=0.381N P=0.325N P=0.438N P=0.279N | |POLY 6 | P=0.239 P=0.122 P=0.409N P=0.370N P=0.598N P=0.215 | |LOGISTIC REGRESSION| P=0.547 P=0.154 P=0.431N P=0.389N P=0.417N P=0.615N | |COCH-ARM / FISHERS | P=0.017N* P=0.235 P=0.412N P=0.330N P=0.412N P=0.069N | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 38 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/49 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/42.87 0/39.94 2/41.66 0/40.71 0/40.99 0/17.60 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.8% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 1/28 (4%) 0/22 (0%) 0/28 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 715 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.887N (e) P=0.209 (e) (e) (e) | |POLY 3 | P=0.396N (e) P=0.230 (e) (e) (e) | |POLY 1.5 | P=0.414N (e) P=0.234 (e) (e) (e) | |POLY 6 | P=0.458N (e) P=0.223 (e) (e) (e) | |LOGISTIC REGRESSION| P=0.854N (e) P=0.213 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.429N (e) P=0.247 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 5/50 (10%) 1/49 (2%) 1/49 (2%) 3/50 (6%) | |POLY-3 RATE (b) | 0/42.87 1/40.38 5/43.05 1/40.91 1/41.42 3/19.34 | |POLY-3 PERCENT (g) | 0.0% 2.5% 11.6% 2.4% 2.4% 15.5% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 1/28 (4%) 0/22 (0%) 0/28 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 600 437 678 602 488 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** P=0.495 P=0.030 * P=0.477 P=0.491 P=0.009 ** | |POLY 3 | P=0.162 P=0.488 P=0.030 * P=0.491 P=0.493 P=0.037 * | |POLY 1.5 | P=0.197 P=0.494 P=0.031 * P=0.493 P=0.495 P=0.062 | |POLY 6 | P=0.239 P=0.478 P=0.029 * P=0.485 P=0.488 P=0.022 * | |LOGISTIC REGRESSION| P=0.587 P=0.522 P=0.032 * P=0.496 P=0.476 P=0.184 | |COCH-ARM / FISHERS | P=0.313 P=0.500 P=0.028 * P=0.495 P=0.495 P=0.121 | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 39 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Glandular | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/49 (4%) 1/49 (2%) 9/50 (18%) | |POLY-3 RATE (b) | 0/42.87 0/39.94 0/41.60 2/41.81 1/41.42 9/23.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.8% 2.4% 39.1% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 0/28 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- 451 602 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P=0.245 P=0.491 P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P=0.231 P=0.493 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P=0.232 P=0.495 P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P=0.227 P=0.488 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.278 P=0.476 P=0.014 * | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.242 P=0.495 P<0.001 ** | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Stomach, Glandular | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/49 (4%) 0/49 (0%) 7/50 (14%) | |POLY-3 RATE (b) | 0/42.87 0/39.94 0/41.60 2/42.19 0/40.99 7/21.66 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.7% 0.0% 32.3% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 0/28 (0%) 0/22 (0%) 0/28 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- 307 --- 405 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P=0.238 (e) P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P=0.233 (e) P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P=0.234 (e) P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P=0.228 (e) P<0.001 ** | |LOGISTIC REGRESSION| P=0.012 * (e) (e) P=0.347 (e) P=0.021 * | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.242 (e) P=0.006 ** | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 40 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thymus | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/48 (0%) 2/48 (4%) 0/46 (0%) 0/48 (0%) 0/50 (0%) 2/49 (4%) | |POLY-3 RATE (b) | 0/41.55 2/39.43 0/37.91 0/39.12 0/41.99 2/18.39 | |POLY-3 PERCENT (g) | 0.0% 5.1% 0.0% 0.0% 0.0% 10.9% | |TERMINAL (d) | 0/32 (0%) 0/21 (0%) 0/25 (0%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- 519 --- --- --- 393 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.028 * P=0.242 (e) (e) (e) P=0.096 | |POLY 3 | P=0.141 P=0.225 (e) (e) (e) P=0.115 | |POLY 1.5 | P=0.130 P=0.231 (e) (e) (e) P=0.160 | |POLY 6 | P=0.336 P=0.216 (e) (e) (e) P=0.079 | |LOGISTIC REGRESSION| P=0.514 P=0.278 (e) (e) (e) P=0.581 | |COCH-ARM / FISHERS | P=0.167 P=0.247 (e) (e) (e) P=0.253 | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thyroid Gland | | Ultimobranchial Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/49 (2%) 2/50 (4%) 0/49 (0%) 0/49 (0%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 1/42.28 2/40.37 0/41.38 0/40.72 1/42.75 2/18.68 | |POLY-3 PERCENT (g) | 2.4% 5.0% 0.0% 0.0% 2.3% 10.7% | |TERMINAL (d) | 0/32 (0%) 1/22 (5%) 0/28 (0%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | 611 605 --- --- 451 552 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.013 * P=0.444 P=0.514N P=0.500N P=0.757 P=0.053 | |POLY 3 | P=0.153 P=0.484 P=0.504N P=0.508N P=0.758N P=0.261 | |POLY 1.5 | P=0.178 P=0.495 P=0.501N P=0.504N P=0.756N P=0.363 | |POLY 6 | P=0.248 P=0.464 P=0.511N P=0.515N P=0.757 P=0.168 | |LOGISTIC REGRESSION| P=0.558 P=0.522 P=0.524N P=0.482N P=0.698 P=0.595 | |COCH-ARM / FISHERS | P=0.270 P=0.508 P=0.500N P=0.500N P=0.747N P=0.508 | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 41 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 22/49 (45%) 9/50 (18%) 24/49 (49%) 15/49 (31%) 20/50 (40%) 10/50 (20%) | |POLY-3 RATE (b) | 22/43.58 9/40.81 24/42.74 15/42.19 20/43.90 10/23.16 | |POLY-3 PERCENT (g) | 50.5% 22.1% 56.2% 35.6% 45.6% 43.2% | |TERMINAL (d) | 19/32 (59%) 6/22 (27%) 19/28 (68%) 8/22 (36%) 15/29 (52%) 0/0 (0%) | |FIRST INCIDENCE | 393 573 518 561 463 352 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.056N P=0.211 P=0.475N P=0.570N P<0.001 ** | |POLY 3 | P=0.449 P=0.004N** P=0.373 P=0.113N P=0.400N P=0.381N | |POLY 1.5 | P=0.281N P=0.004N** P=0.398 P=0.113N P=0.391N P=0.090N | |POLY 6 | P=0.181 P=0.006N** P=0.330 P=0.116N P=0.422N P=0.313 | |LOGISTIC REGRESSION| P=0.138 P=0.006N** P=0.390 P=0.117N P=0.402N P=0.625N | |COCH-ARM / FISHERS | P=0.031N* P=0.004N** P=0.420 P=0.105N P=0.386N P=0.007N** | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Uterus | | Hydrometra | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/50 (10%) 7/50 (14%) 0/50 (0%) 6/50 (12%) 6/50 (12%) 6/50 (12%) | |POLY-3 RATE (b) | 5/43.24 7/41.97 0/41.60 6/41.89 6/42.56 6/21.54 | |POLY-3 PERCENT (g) | 11.6% 16.7% 0.0% 14.3% 14.1% 27.9% | |TERMINAL (d) | 4/33 (12%) 0/22 (0%) 0/28 (0%) 3/22 (14%) 3/29 (10%) 0/0 (0%) | |FIRST INCIDENCE | 626 541 --- 451 654 407 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.245 P=0.048N* P=0.313 P=0.424 P=0.002 ** | |POLY 3 | P=0.048 * P=0.357 P=0.033N* P=0.478 P=0.489 P=0.119 | |POLY 1.5 | P=0.111 P=0.368 P=0.032N* P=0.485 P=0.497 P=0.258 | |POLY 6 | P=0.029 * P=0.339 P=0.037N* P=0.459 P=0.470 P=0.035 * | |LOGISTIC REGRESSION| P=0.320 P=0.382 P=0.037N* P=0.486 P=0.478 P=0.519 | |COCH-ARM / FISHERS | P=0.304 P=0.380 P=0.028N* P=0.500 P=0.500 P=0.500 | |=================================================================================================================================| Date: 12/15/00 EXPERIMENT: 05161 TEST: 05 Page 42 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - RIDDELLIINE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Uterus | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/50 (8%) 3/50 (6%) 7/50 (14%) 5/50 (10%) 2/50 (4%) 9/50 (18%) | |POLY-3 RATE (b) | 4/42.87 3/39.99 7/42.39 5/41.10 2/42.34 9/23.06 | |POLY-3 PERCENT (g) | 9.3% 7.5% 16.5% 12.2% 4.7% 39.0% | |TERMINAL (d) | 4/33 (12%) 2/22 (9%) 6/28 (21%) 3/22 (14%) 1/29 (3%) 0/0 (0%) | |FIRST INCIDENCE | 729 (T) 718 437 660 630 472 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.603 P=0.180 P=0.288 P=0.390N P<0.001 ** | |POLY 3 | P=0.017 * P=0.538N P=0.252 P=0.473 P=0.342N P=0.007 ** | |POLY 1.5 | P=0.027 * P=0.520N P=0.260 P=0.482 P=0.338N P=0.028 * | |POLY 6 | P=0.021 * P=0.570N P=0.236 P=0.456 P=0.354N P<0.001 ** | |LOGISTIC REGRESSION| P=0.017 * P=0.648 P=0.242 P=0.405 P=0.360N P=0.043 * | |COCH-ARM / FISHERS | P=0.070 P=0.500N P=0.262 P=0.500 P=0.339N P=0.117 | |=================================================================================================================================| | | | | | Females | |Dose | 0 0.01 0.033 0.1 0.33 1.0 | | | MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY MG/KG/DY | |=================================================================================================================================| | | |Uterus | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 0/42.87 0/39.94 2/41.60 0/40.79 1/42.25 0/17.60 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.8% 0.0% 2.4% 0.0% | |TERMINAL (d) | 0/33 (0%) 0/22 (0%) 2/28 (7%) 0/22 (0%) 0/29 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- 729 (T) --- 658 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.842 (e) P=0.202 (e) P=0.484 (e) | |POLY 3 | P=0.620 (e) P=0.230 (e) P=0.497 (e) | |POLY 1.5 | P=0.578N (e) P=0.234 (e) P=0.499 (e) | |POLY 6 | P=0.544 (e) P=0.223 (e) P=0.492 (e) | |LOGISTIC REGRESSION| P=0.846 (e) P=0.202 (e) P=0.498 (e) | |COCH-ARM / FISHERS | P=0.496N (e) P=0.247 (e) P=0.500 (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). --multipart-boundary Content-type: text/plain Range: bytes 362693-362693/362693 --multipart-boundary--