TDMS Study 96007-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 11/25/02 EXPERIMENT: 96007 TEST: 03 TIME: 12:43:22 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007G PATHOLOGIST: SELLS, DONALD CAS: 1746-01-6 ------------------------------------------------------------------------------------------------------------------------------------ CONTROL VS HIGH DOSE AND STOP GRP. REASONS FOR REMOVAL: 25018 Dosing Accident 25019 Moribund Sacrifice 25020 Natural Death 25021 Terminal Sacrifice REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 001 0 NG/KG INCLUDE 006 100 NG/KG INCLUDE 007 100 NG/ KG/STOP NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 11/25/02 EXPERIMENT: 96007 TEST: 03 TIME: 12:43:22 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007G PATHOLOGIST: SELLS, DONALD CAS: 1746-01-6 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TOXIC EQUIVALENCY FACTOR EVALUATION =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Angiectasis Atrophy Degeneration Cystic Hyperplasia Hypertrophy Necrosis Vacuolization Cytoplasmic Adrenal Medulla Hyperplasia Bone Marrow Hyperplasia Brain Mineralization Clitoral Gland Inflammation Clitoral Gland: Duct Cyst Eye: Retina Atrophy Harderian Gland Inflammation Heart Cardiomyopathy Heart: Atrium Thrombosis Intestine Large, Colon Parasite Metazoan Intestine Large, Rectum Parasite Metazoan Kidney Accumulation, Hyaline Droplet Casts Protein Cyst Inflammation Inflammation Chronic Mineralization Nephropathy Kidney: Pelvis Dilatation Inflammation Kidney: Transitional Epithelium Hyperplasia Liver Angiectasis Basophilic Focus Cholangiofibrosis Clear Cell Focus Congestion Cytoplasmic Alteration Degeneration Cystic Eosinophilic Focus Fatty Change Diffuse Fatty Change Focal Hematopoietic Cell Proliferation Inflammation Mixed Cell Focus Necrosis Pigmentation Regeneration Toxic Hepatopathy Liver: Artery Inflammation Chronic Liver: Bile Duct Cyst Fibrosis NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 11/25/02 EXPERIMENT: 96007 TEST: 03 TIME: 12:43:22 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007G PATHOLOGIST: SELLS, DONALD CAS: 1746-01-6 Hyperplasia Liver: Centrilobular Degeneration Liver: Hepatocyte Hypertrophy Multinucleated Liver: Oval Cell Hyperplasia Liver: Portal Fibrosis Lung Hemorrhage Infiltration Cellular Histiocyte Inflammation Granulomatous Metaplasia Lung: Alveolar Epithelium Hyperplasia Metaplasia Bronchiolar Lymph Node, Mandibular Ectasia Hyperplasia Hyperplasia Lymphoid Lymph Node, Mesenteric Hyperplasia Lymph Node: Lumbar Ectasia Hyperplasia Lymph Node: Mediastinal Ectasia Hemorrhage Mammary Gland Cyst Hyperplasia Mesentery: Artery Inflammation Chronic Nose Inflammation Nose: Nasolacrimal Duct Inflammation Nose: Septum Inflammation Nose: Turbinate, Septum Inflammation Oral Mucosa: Gingival Hyperplasia Ovary Atrophy Cyst Pancreas Inflammation Chronic Pancreas: Acinus Atrophy Hyperplasia Vacuolization Cytoplasmic Pancreas: Artery Inflammation Chronic Pituitary Gland Angiectasis Vacuolization Cytoplasmic Pituitary Gland: Pars Distalis Hyperplasia Pituitary Gland: Pars Intermedia Hyperplasia Salivary Glands Atrophy Skin Cyst Epithelial Inclusion Spleen Hematopoietic Cell Proliferation Hyperplasia Lymphoid Pigmentation Spleen: Lymphoid Follicle Atrophy Stomach, Forestomach Hyperkeratosis Hyperplasia Inflammation Ulcer Stomach, Glandular Mineralization Ulcer Thymus Atrophy Thyroid Gland: C-Cell Hyperplasia Thyroid Gland: Follicular Cell Hyperplasia Hypertrophy Tooth: Peridontal Tissue Inflammation Urinary Bladder Inflammation Urinary Bladder: Transitional Epithelium NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD) DATE: 11/25/02 EXPERIMENT: 96007 TEST: 03 TIME: 12:43:22 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007G PATHOLOGIST: SELLS, DONALD CAS: 1746-01-6 Hyperplasia Uterus Inflammation Metaplasia Uterus: Endometrium Hyperplasia Cystic =============================================================== Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/53 (21%) 26/103 (25%) | |POLY-3 RATE (b) | 11/40.84 26/83.93 | |POLY-3 PERCENT (g) | 26.9% 31.0% | |TERMINAL (d) | 6/25 (24%) 14/42 (33%) | |FIRST INCIDENCE | 645 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.252 P=0.252 | |POLY 3 | P=0.397 P=0.372 | |POLY 1.5 | P=0.393 P=0.368 | |POLY 6 | P=0.372 P=0.345 | |LOGISTIC REGRESSION| P=0.387 P=0.387 | |COCH-ARM / FISHERS | P=0.335 P=0.339 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 31/103 (30%) | |POLY-3 RATE (b) | 2/39.86 31/85.18 | |POLY-3 PERCENT (g) | 5.0% 36.4% | |TERMINAL (d) | 1/25 (4%) 15/42 (36%) | |FIRST INCIDENCE | 646 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/53 (21%) 34/103 (33%) | |POLY-3 RATE (b) | 11/41.19 34/86.31 | |POLY-3 PERCENT (g) | 26.7% 39.4% | |TERMINAL (d) | 4/25 (16%) 16/42 (38%) | |FIRST INCIDENCE | 646 474 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.069 P=0.069 | |POLY 3 | P=0.132 P=0.100 | |POLY 1.5 | P=0.126 P=0.095 | |POLY 6 | P=0.124 P=0.092 | |LOGISTIC REGRESSION| P=0.100 P=0.100 | |COCH-ARM / FISHERS | P=0.079 P=0.077 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 16/53 (30%) 50/103 (49%) | |POLY-3 RATE (b) | 16/41.46 50/88.21 | |POLY-3 PERCENT (g) | 38.6% 56.7% | |TERMINAL (d) | 10/25 (40%) 27/42 (64%) | |FIRST INCIDENCE | 487 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.015 * P=0.015 * | |POLY 3 | P=0.052 P=0.032 * | |POLY 1.5 | P=0.047 * P=0.029 * | |POLY 6 | P=0.049 * P=0.029 * | |LOGISTIC REGRESSION| P=0.031 * P=0.031 * | |COCH-ARM / FISHERS | P=0.021 * P=0.021 * | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 41/53 (77%) 93/103 (90%) | |POLY-3 RATE (b) | 41/44.21 93/99.14 | |POLY-3 PERCENT (g) | 92.8% 93.8% | |TERMINAL (d) | 25/25 (100%) 41/42 (98%) | |FIRST INCIDENCE | 474 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.061 P=0.061 | |POLY 3 | P=0.529 P=0.501 | |POLY 1.5 | P=0.260 P=0.216 | |POLY 6 | P=0.497N P=0.455N | |LOGISTIC REGRESSION| P=0.091 P=0.091 | |COCH-ARM / FISHERS | P=0.025 * P=0.027 * | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 4/103 (4%) | |POLY-3 RATE (b) | 0/39.55 4/82.39 | |POLY-3 PERCENT (g) | 0.0% 4.9% | |TERMINAL (d) | 0/25 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 578 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.194 P=0.194 | |POLY 3 | P=0.199 P=0.150 | |POLY 1.5 | P=0.195 P=0.148 | |POLY 6 | P=0.198 P=0.149 | |LOGISTIC REGRESSION| P=0.155 P=0.155 | |COCH-ARM / FISHERS | P=0.179 P=0.186 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/53 (21%) 28/103 (27%) | |POLY-3 RATE (b) | 11/40.73 28/86.20 | |POLY-3 PERCENT (g) | 27.0% 32.5% | |TERMINAL (d) | 9/25 (36%) 12/42 (29%) | |FIRST INCIDENCE | 366 345 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.194 P=0.194 | |POLY 3 | P=0.343 P=0.313 | |POLY 1.5 | P=0.321 P=0.289 | |POLY 6 | P=0.359 P=0.329 | |LOGISTIC REGRESSION| P=0.285 P=0.285 | |COCH-ARM / FISHERS | P=0.247 P=0.249 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 19/53 (36%) 24/103 (23%) | |POLY-3 RATE (b) | 19/41.29 24/84.44 | |POLY-3 PERCENT (g) | 46.0% 28.4% | |TERMINAL (d) | 11/25 (44%) 11/42 (26%) | |FIRST INCIDENCE | 487 578 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.137N P=0.137N | |POLY 3 | P=0.051N P=0.031N* | |POLY 1.5 | P=0.058N P=0.037N* | |POLY 6 | P=0.050N P=0.031N* | |LOGISTIC REGRESSION| P=0.044N* P=0.044N* | |COCH-ARM / FISHERS | P=0.071N P=0.072N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 36/53 (68%) 79/103 (77%) | |POLY-3 RATE (b) | 36/52.64 79/100.3 | |POLY-3 PERCENT (g) | 68.4% 78.8% | |TERMINAL (d) | 9/25 (36%) 26/42 (62%) | |FIRST INCIDENCE | 169 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.236 P=0.236 | |POLY 3 | P=0.124 P=0.095 | |POLY 1.5 | P=0.147 P=0.116 | |POLY 6 | P=0.096 P=0.070 | |LOGISTIC REGRESSION| P=0.123 P=0.123 | |COCH-ARM / FISHERS | P=0.162 P=0.162 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Brain | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/103 (2%) | |POLY-3 RATE (b) | 0/39.55 2/80.75 | |POLY-3 PERCENT (g) | 0.0% 2.5% | |TERMINAL (d) | 0/25 (0%) 2/42 (5%) | |FIRST INCIDENCE | --- 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.358 P=0.358 | |POLY 3 | P=0.373 P=0.314 | |POLY 1.5 | P=0.372 P=0.313 | |POLY 6 | P=0.369 P=0.310 | |LOGISTIC REGRESSION| (e) P=0.358 | |COCH-ARM / FISHERS | P=0.394 P=0.434 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 41/50 (82%) 61/102 (60%) | |POLY-3 RATE (b) | 41/46.36 61/93.09 | |POLY-3 PERCENT (g) | 88.4% 65.5% | |TERMINAL (d) | 22/25 (88%) 27/42 (64%) | |FIRST INCIDENCE | 169 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.128N P=0.128N | |POLY 3 | P=0.004N** P<0.001N** | |POLY 1.5 | P=0.005N** P=0.002N** | |POLY 6 | P=0.005N** P=0.002N** | |LOGISTIC REGRESSION| P=0.005N** P=0.005N** | |COCH-ARM / FISHERS | P=0.005N** P=0.004N** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Clitoral Gland: Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 34/50 (68%) 83/102 (81%) | |POLY-3 RATE (b) | 34/44.15 83/97.26 | |POLY-3 PERCENT (g) | 77.0% 85.3% | |TERMINAL (d) | 19/25 (76%) 35/42 (83%) | |FIRST INCIDENCE | 169 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.047 * P=0.047 * | |POLY 3 | P=0.175 P=0.133 | |POLY 1.5 | P=0.141 P=0.103 | |POLY 6 | P=0.195 P=0.152 | |LOGISTIC REGRESSION| P=0.079 P=0.079 | |COCH-ARM / FISHERS | P=0.051 P=0.053 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Eye: Retina | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 12/103 (12%) | |POLY-3 RATE (b) | 5/39.55 12/81.41 | |POLY-3 PERCENT (g) | 12.6% 14.7% | |TERMINAL (d) | 5/25 (20%) 8/42 (19%) | |FIRST INCIDENCE | 731 (T) 645 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.341 P=0.341 | |POLY 3 | P=0.472 P=0.450 | |POLY 1.5 | P=0.466 P=0.444 | |POLY 6 | P=0.465 P=0.442 | |LOGISTIC REGRESSION| P=0.431 P=0.431 | |COCH-ARM / FISHERS | P=0.441 P=0.450 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Harderian Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/53 (23%) 15/103 (15%) | |POLY-3 RATE (b) | 12/42.07 15/83.10 | |POLY-3 PERCENT (g) | 28.5% 18.1% | |TERMINAL (d) | 6/25 (24%) 7/42 (17%) | |FIRST INCIDENCE | 366 546 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.214N P=0.214N | |POLY 3 | P=0.147N P=0.114N | |POLY 1.5 | P=0.147N P=0.114N | |POLY 6 | P=0.158N P=0.125N | |LOGISTIC REGRESSION| P=0.127N P=0.127N | |COCH-ARM / FISHERS | P=0.149N P=0.149N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/53 (19%) 58/102 (57%) | |POLY-3 RATE (b) | 10/41.81 58/89.75 | |POLY-3 PERCENT (g) | 23.9% 64.6% | |TERMINAL (d) | 6/25 (24%) 24/42 (57%) | |FIRST INCIDENCE | 169 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Heart: Atrium | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/102 (2%) | |POLY-3 RATE (b) | 0/39.55 2/80.62 | |POLY-3 PERCENT (g) | 0.0% 2.5% | |TERMINAL (d) | 0/25 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.406 P=0.406 | |POLY 3 | P=0.372 P=0.314 | |POLY 1.5 | P=0.371 P=0.313 | |POLY 6 | P=0.369 P=0.312 | |LOGISTIC REGRESSION| P=0.354 P=0.354 | |COCH-ARM / FISHERS | P=0.391 P=0.432 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Intestine Large, Colon | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 3/100 (3%) | |POLY-3 RATE (b) | 1/39.56 3/79.41 | |POLY-3 PERCENT (g) | 2.5% 3.8% | |TERMINAL (d) | 0/25 (0%) 1/42 (2%) | |FIRST INCIDENCE | 701 614 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.550 P=0.550 | |POLY 3 | P=0.533 P=0.503 | |POLY 1.5 | P=0.532 P=0.502 | |POLY 6 | P=0.529 P=0.499 | |LOGISTIC REGRESSION| P=0.565 P=0.565 | |COCH-ARM / FISHERS | P=0.556 P=0.577 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Intestine Large, Rectum | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/52 (12%) 6/103 (6%) | |POLY-3 RATE (b) | 6/39.78 6/81.39 | |POLY-3 PERCENT (g) | 15.1% 7.4% | |TERMINAL (d) | 2/25 (8%) 4/42 (10%) | |FIRST INCIDENCE | 645 641 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.235N P=0.235N | |POLY 3 | P=0.171N P=0.131N | |POLY 1.5 | P=0.171N P=0.131N | |POLY 6 | P=0.182N P=0.143N | |LOGISTIC REGRESSION| P=0.156N P=0.156N | |COCH-ARM / FISHERS | P=0.174N P=0.173N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Kidney | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/103 (2%) | |POLY-3 RATE (b) | 0/39.55 2/81.60 | |POLY-3 PERCENT (g) | 0.0% 2.5% | |TERMINAL (d) | 0/25 (0%) 1/42 (2%) | |FIRST INCIDENCE | --- 394 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.386 P=0.386 | |POLY 3 | P=0.375 P=0.316 | |POLY 1.5 | P=0.374 P=0.314 | |POLY 6 | P=0.372 P=0.313 | |LOGISTIC REGRESSION| P=0.332 P=0.332 | |COCH-ARM / FISHERS | P=0.394 P=0.434 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Kidney | | Casts Protein | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 2/103 (2%) | |POLY-3 RATE (b) | 3/40.58 2/81.71 | |POLY-3 PERCENT (g) | 7.4% 2.5% | |TERMINAL (d) | 0/25 (0%) 0/42 (0%) | |FIRST INCIDENCE | 512 578 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.206N P=0.206N | |POLY 3 | P=0.212N P=0.166N | |POLY 1.5 | P=0.212N P=0.166N | |POLY 6 | P=0.218N P=0.173N | |LOGISTIC REGRESSION| P=0.252N P=0.252N | |COCH-ARM / FISHERS | P=0.221N P=0.216N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Kidney | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/103 (1%) | |POLY-3 RATE (b) | 2/39.90 1/81.20 | |POLY-3 PERCENT (g) | 5.0% 1.2% | |TERMINAL (d) | 1/25 (4%) 0/42 (0%) | |FIRST INCIDENCE | 631 598 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.283N P=0.283N | |POLY 3 | P=0.255N P=0.202N | |POLY 1.5 | P=0.256N P=0.203N | |POLY 6 | P=0.259N P=0.207N | |LOGISTIC REGRESSION| P=0.276N P=0.276N | |COCH-ARM / FISHERS | P=0.277N P=0.266N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Kidney | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/103 (2%) | |POLY-3 RATE (b) | 0/39.55 2/81.41 | |POLY-3 PERCENT (g) | 0.0% 2.5% | |TERMINAL (d) | 0/25 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 604 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.401 P=0.401 | |POLY 3 | P=0.375 P=0.315 | |POLY 1.5 | P=0.373 P=0.314 | |POLY 6 | P=0.372 P=0.313 | |LOGISTIC REGRESSION| P=0.386 P=0.386 | |COCH-ARM / FISHERS | P=0.394 P=0.434 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Kidney | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 0/103 (0%) | |POLY-3 RATE (b) | 5/40.43 0/80.75 | |POLY-3 PERCENT (g) | 12.4% 0.0% | |TERMINAL (d) | 4/25 (16%) 0/42 (0%) | |FIRST INCIDENCE | 361 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.006N** P=0.006N** | |POLY 3 | P=0.004N** P<0.001N** | |POLY 1.5 | P=0.004N** P<0.001N** | |POLY 6 | P=0.004N** P=0.002N** | |LOGISTIC REGRESSION| P=0.003N** P=0.003N** | |COCH-ARM / FISHERS | P=0.004N** P=0.004N** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 40/53 (75%) 84/103 (82%) | |POLY-3 RATE (b) | 40/47.18 84/97.90 | |POLY-3 PERCENT (g) | 84.8% 85.8% | |TERMINAL (d) | 22/25 (88%) 34/42 (81%) | |FIRST INCIDENCE | 169 394 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.215 P=0.215 | |POLY 3 | P=0.518 P=0.502 | |POLY 1.5 | P=0.395 P=0.368 | |POLY 6 | P=0.510N P=0.491N | |LOGISTIC REGRESSION| P=0.343 P=0.343 | |COCH-ARM / FISHERS | P=0.248 P=0.246 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 34/53 (64%) 93/103 (90%) | |POLY-3 RATE (b) | 34/45.60 93/97.74 | |POLY-3 PERCENT (g) | 74.6% 95.2% | |TERMINAL (d) | 21/25 (84%) 41/42 (98%) | |FIRST INCIDENCE | 169 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004 ** P=0.004 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Kidney: Pelvis | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/103 (1%) | |POLY-3 RATE (b) | 2/40.16 1/81.46 | |POLY-3 PERCENT (g) | 5.0% 1.2% | |TERMINAL (d) | 1/25 (4%) 0/42 (0%) | |FIRST INCIDENCE | 533 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.272N P=0.272N | |POLY 3 | P=0.256N P=0.203N | |POLY 1.5 | P=0.257N P=0.203N | |POLY 6 | P=0.260N P=0.208N | |LOGISTIC REGRESSION| P=0.327N P=0.327N | |COCH-ARM / FISHERS | P=0.277N P=0.266N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Kidney: Pelvis | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 2/103 (2%) | |POLY-3 RATE (b) | 2/39.55 2/80.87 | |POLY-3 PERCENT (g) | 5.1% 2.5% | |TERMINAL (d) | 2/25 (8%) 1/42 (2%) | |FIRST INCIDENCE | 731 (T) 701 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.482N P=0.482N | |POLY 3 | P=0.398N P=0.353N | |POLY 1.5 | P=0.400N P=0.355N | |POLY 6 | P=0.403N P=0.359N | |LOGISTIC REGRESSION| P=0.448N P=0.448N | |COCH-ARM / FISHERS | P=0.440N P=0.419N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Kidney: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 16/103 (16%) | |POLY-3 RATE (b) | 3/40.54 16/83.25 | |POLY-3 PERCENT (g) | 7.4% 19.2% | |TERMINAL (d) | 2/25 (8%) 7/42 (17%) | |FIRST INCIDENCE | 169 584 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.057 P=0.057 | |POLY 3 | P=0.090 P=0.062 | |POLY 1.5 | P=0.087 P=0.060 | |POLY 6 | P=0.089 P=0.061 | |LOGISTIC REGRESSION| P=0.067 P=0.067 | |COCH-ARM / FISHERS | P=0.063 P=0.058 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 9/103 (9%) | |POLY-3 RATE (b) | 2/39.55 9/81.34 | |POLY-3 PERCENT (g) | 5.1% 11.1% | |TERMINAL (d) | 2/25 (8%) 7/42 (17%) | |FIRST INCIDENCE | 731 (T) 561 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.159 P=0.159 | |POLY 3 | P=0.239 P=0.198 | |POLY 1.5 | P=0.237 P=0.197 | |POLY 6 | P=0.232 P=0.191 | |LOGISTIC REGRESSION| P=0.207 P=0.207 | |COCH-ARM / FISHERS | P=0.207 P=0.211 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/53 (23%) 24/103 (23%) | |POLY-3 RATE (b) | 12/42.33 24/83.76 | |POLY-3 PERCENT (g) | 28.4% 28.7% | |TERMINAL (d) | 4/25 (16%) 10/42 (24%) | |FIRST INCIDENCE | 492 520 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.462 P=0.462 | |POLY 3 | P=0.550 P=0.542 | |POLY 1.5 | P=0.560 P=0.554 | |POLY 6 | P=0.510 P=0.497 | |LOGISTIC REGRESSION| P=0.564N P=0.564N | |COCH-ARM / FISHERS | P=0.543 P=0.548 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Cholangiofibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 32/103 (31%) | |POLY-3 RATE (b) | 1/39.86 32/85.28 | |POLY-3 PERCENT (g) | 2.5% 37.5% | |TERMINAL (d) | 0/25 (0%) 14/42 (33%) | |FIRST INCIDENCE | 645 581 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 10/103 (10%) | |POLY-3 RATE (b) | 5/40.18 10/80.75 | |POLY-3 PERCENT (g) | 12.4% 12.4% | |TERMINAL (d) | 3/25 (12%) 10/42 (24%) | |FIRST INCIDENCE | 548 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.499 P=0.499 | |POLY 3 | P=0.583N P=0.574N | |POLY 1.5 | P=0.580N P=0.571N | |POLY 6 | P=0.572 P=0.562 | |LOGISTIC REGRESSION| P=0.594 P=0.594 | |COCH-ARM / FISHERS | P=0.592 P=0.624N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 2/103 (2%) | |POLY-3 RATE (b) | 2/39.85 2/82.01 | |POLY-3 PERCENT (g) | 5.0% 2.4% | |TERMINAL (d) | 1/25 (4%) 0/42 (0%) | |FIRST INCIDENCE | 648 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.443N P=0.443N | |POLY 3 | P=0.396N P=0.351N | |POLY 1.5 | P=0.398N P=0.354N | |POLY 6 | P=0.401N P=0.357N | |LOGISTIC REGRESSION| P=0.492N P=0.492N | |COCH-ARM / FISHERS | P=0.440N P=0.419N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Cytoplasmic Alteration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 3/103 (3%) | |POLY-3 RATE (b) | 0/39.55 3/80.75 | |POLY-3 PERCENT (g) | 0.0% 3.7% | |TERMINAL (d) | 0/25 (0%) 3/42 (7%) | |FIRST INCIDENCE | --- 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.226 P=0.226 | |POLY 3 | P=0.264 P=0.211 | |POLY 1.5 | P=0.264 P=0.210 | |POLY 6 | P=0.259 P=0.207 | |LOGISTIC REGRESSION| (e) P=0.226 | |COCH-ARM / FISHERS | P=0.261 P=0.285 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 4/103 (4%) | |POLY-3 RATE (b) | 0/39.55 4/81.49 | |POLY-3 PERCENT (g) | 0.0% 4.9% | |TERMINAL (d) | 0/25 (0%) 2/42 (5%) | |FIRST INCIDENCE | --- 610 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.166 P=0.166 | |POLY 3 | P=0.196 P=0.148 | |POLY 1.5 | P=0.194 P=0.146 | |POLY 6 | P=0.193 P=0.145 | |LOGISTIC REGRESSION| P=0.187 P=0.187 | |COCH-ARM / FISHERS | P=0.179 P=0.186 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/53 (21%) 71/103 (69%) | |POLY-3 RATE (b) | 11/40.67 71/95.23 | |POLY-3 PERCENT (g) | 27.1% 74.6% | |TERMINAL (d) | 6/25 (24%) 30/42 (71%) | |FIRST INCIDENCE | 645 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Fatty Change Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 58/103 (56%) | |POLY-3 RATE (b) | 0/39.55 58/92.31 | |POLY-3 PERCENT (g) | 0.0% 62.8% | |TERMINAL (d) | 0/25 (0%) 22/42 (52%) | |FIRST INCIDENCE | --- 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Fatty Change Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 10/103 (10%) | |POLY-3 RATE (b) | 2/39.69 10/81.52 | |POLY-3 PERCENT (g) | 5.0% 12.3% | |TERMINAL (d) | 1/25 (4%) 7/42 (17%) | |FIRST INCIDENCE | 694 604 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.122 P=0.122 | |POLY 3 | P=0.191 P=0.152 | |POLY 1.5 | P=0.190 P=0.151 | |POLY 6 | P=0.183 P=0.144 | |LOGISTIC REGRESSION| P=0.164 P=0.164 | |COCH-ARM / FISHERS | P=0.159 P=0.159 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 4/103 (4%) | |POLY-3 RATE (b) | 1/39.86 4/81.74 | |POLY-3 PERCENT (g) | 2.5% 4.9% | |TERMINAL (d) | 0/25 (0%) 1/42 (2%) | |FIRST INCIDENCE | 646 599 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.421 P=0.421 | |POLY 3 | P=0.424 P=0.385 | |POLY 1.5 | P=0.422 P=0.383 | |POLY 6 | P=0.418 P=0.379 | |LOGISTIC REGRESSION| P=0.427 P=0.427 | |COCH-ARM / FISHERS | P=0.424 P=0.446 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 33/53 (62%) 92/103 (89%) | |POLY-3 RATE (b) | 33/47.21 92/99.30 | |POLY-3 PERCENT (g) | 69.9% 92.6% | |TERMINAL (d) | 17/25 (68%) 38/42 (91%) | |FIRST INCIDENCE | 351 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.006 ** P=0.006 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 30/53 (57%) 50/103 (49%) | |POLY-3 RATE (b) | 30/41.81 50/86.61 | |POLY-3 PERCENT (g) | 71.8% 57.7% | |TERMINAL (d) | 22/25 (88%) 33/42 (79%) | |FIRST INCIDENCE | 492 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.429N P=0.429N | |POLY 3 | P=0.094N P=0.066N | |POLY 1.5 | P=0.125N P=0.094N | |POLY 6 | P=0.078N P=0.053N | |LOGISTIC REGRESSION| P=0.106N P=0.106N | |COCH-ARM / FISHERS | P=0.216N P=0.216N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 25/103 (24%) | |POLY-3 RATE (b) | 1/39.67 25/87.58 | |POLY-3 PERCENT (g) | 2.5% 28.6% | |TERMINAL (d) | 0/25 (0%) 3/42 (7%) | |FIRST INCIDENCE | 701 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P=0.002 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P=0.002 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 98/103 (95%) | |POLY-3 RATE (b) | 4/40.41 98/100.8 | |POLY-3 PERCENT (g) | 9.9% 97.2% | |TERMINAL (d) | 1/25 (4%) 41/42 (98%) | |FIRST INCIDENCE | 533 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Regeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 36/103 (35%) | |POLY-3 RATE (b) | 0/39.55 36/87.12 | |POLY-3 PERCENT (g) | 0.0% 41.3% | |TERMINAL (d) | 0/25 (0%) 14/42 (33%) | |FIRST INCIDENCE | --- 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver | | Toxic Hepatopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 69/103 (67%) | |POLY-3 RATE (b) | 0/39.55 69/93.19 | |POLY-3 PERCENT (g) | 0.0% 74.0% | |TERMINAL (d) | 0/25 (0%) 30/42 (71%) | |FIRST INCIDENCE | --- 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/103 (2%) | |POLY-3 RATE (b) | 0/39.55 2/81.47 | |POLY-3 PERCENT (g) | 0.0% 2.5% | |TERMINAL (d) | 0/25 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 581 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.407 P=0.407 | |POLY 3 | P=0.375 P=0.315 | |POLY 1.5 | P=0.373 P=0.314 | |POLY 6 | P=0.372 P=0.313 | |LOGISTIC REGRESSION| P=0.379 P=0.379 | |COCH-ARM / FISHERS | P=0.394 P=0.434 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 24 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 27/103 (26%) | |POLY-3 RATE (b) | 3/39.85 27/83.11 | |POLY-3 PERCENT (g) | 7.5% 32.5% | |TERMINAL (d) | 2/25 (8%) 17/42 (41%) | |FIRST INCIDENCE | 648 612 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P=0.004 ** P=0.002 ** | |POLY 1.5 | P=0.004 ** P=0.002 ** | |POLY 6 | P=0.004 ** P<0.001 ** | |LOGISTIC REGRESSION| P=0.002 ** P=0.002 ** | |COCH-ARM / FISHERS | P=0.002 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 9/103 (9%) | |POLY-3 RATE (b) | 0/39.55 9/81.65 | |POLY-3 PERCENT (g) | 0.0% 11.0% | |TERMINAL (d) | 0/25 (0%) 6/42 (14%) | |FIRST INCIDENCE | --- 598 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.026 * P=0.026 * | |POLY 3 | P=0.047 * P=0.027 * | |POLY 1.5 | P=0.046 * P=0.027 * | |POLY 6 | P=0.045 * P=0.025 * | |LOGISTIC REGRESSION| P=0.034 * P=0.034 * | |COCH-ARM / FISHERS | P=0.032 * P=0.021 * | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 25 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 60/103 (58%) | |POLY-3 RATE (b) | 5/40.16 60/92.33 | |POLY-3 PERCENT (g) | 12.5% 65.0% | |TERMINAL (d) | 4/25 (16%) 23/42 (55%) | |FIRST INCIDENCE | 533 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver: Centrilobular | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 5/103 (5%) | |POLY-3 RATE (b) | 2/39.97 5/82.04 | |POLY-3 PERCENT (g) | 5.0% 6.1% | |TERMINAL (d) | 0/25 (0%) 1/42 (2%) | |FIRST INCIDENCE | 648 610 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.531 P=0.531 | |POLY 3 | P=0.536 P=0.513 | |POLY 1.5 | P=0.533 P=0.510 | |POLY 6 | P=0.530 P=0.507 | |LOGISTIC REGRESSION| P=0.549 P=0.549 | |COCH-ARM / FISHERS | P=0.540 P=0.556 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 26 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 74/103 (72%) | |POLY-3 RATE (b) | 0/39.55 74/95.87 | |POLY-3 PERCENT (g) | 0.0% 77.2% | |TERMINAL (d) | 0/25 (0%) 30/42 (71%) | |FIRST INCIDENCE | --- 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Multinucleated | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 83/103 (81%) | |POLY-3 RATE (b) | 0/39.55 83/95.86 | |POLY-3 PERCENT (g) | 0.0% 86.6% | |TERMINAL (d) | 0/25 (0%) 36/42 (86%) | |FIRST INCIDENCE | --- 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 27 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver: Oval Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 54/103 (52%) | |POLY-3 RATE (b) | 0/39.55 54/91.16 | |POLY-3 PERCENT (g) | 0.0% 59.2% | |TERMINAL (d) | 0/25 (0%) 22/42 (52%) | |FIRST INCIDENCE | --- 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Liver: Portal | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 28/103 (27%) | |POLY-3 RATE (b) | 0/39.55 28/85.88 | |POLY-3 PERCENT (g) | 0.0% 32.6% | |TERMINAL (d) | 0/25 (0%) 11/42 (26%) | |FIRST INCIDENCE | --- 474 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 28 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lung | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/102 (2%) | |POLY-3 RATE (b) | 0/39.55 2/80.64 | |POLY-3 PERCENT (g) | 0.0% 2.5% | |TERMINAL (d) | 0/25 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 474 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.404 P=0.404 | |POLY 3 | P=0.373 P=0.314 | |POLY 1.5 | P=0.371 P=0.313 | |POLY 6 | P=0.369 P=0.312 | |LOGISTIC REGRESSION| P=0.350 P=0.350 | |COCH-ARM / FISHERS | P=0.391 P=0.432 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 41/53 (77%) 91/102 (89%) | |POLY-3 RATE (b) | 41/48.55 91/95.84 | |POLY-3 PERCENT (g) | 84.5% 95.0% | |TERMINAL (d) | 19/25 (76%) 39/42 (93%) | |FIRST INCIDENCE | 351 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.120 P=0.120 | |POLY 3 | P=0.033 * P=0.018 * | |POLY 1.5 | P=0.043 * P=0.026 * | |POLY 6 | P=0.028 * P=0.015 * | |LOGISTIC REGRESSION| P=0.118 P=0.118 | |COCH-ARM / FISHERS | P=0.042 * P=0.044 * | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 29 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lung | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/102 (0%) | |POLY-3 RATE (b) | 2/39.90 0/79.79 | |POLY-3 PERCENT (g) | 5.0% 0.0% | |TERMINAL (d) | 0/25 (0%) 0/42 (0%) | |FIRST INCIDENCE | 645 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.120N P=0.120N | |POLY 3 | P=0.105N P=0.066N | |POLY 1.5 | P=0.106N P=0.066N | |POLY 6 | P=0.108N P=0.068N | |LOGISTIC REGRESSION| P=0.104N P=0.104N | |COCH-ARM / FISHERS | P=0.110N P=0.115N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lung | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 9/102 (9%) | |POLY-3 RATE (b) | 1/39.55 9/82.29 | |POLY-3 PERCENT (g) | 2.5% 10.9% | |TERMINAL (d) | 1/25 (4%) 2/42 (5%) | |FIRST INCIDENCE | 731 (T) 561 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.100 P=0.100 | |POLY 3 | P=0.126 P=0.090 | |POLY 1.5 | P=0.121 P=0.087 | |POLY 6 | P=0.126 P=0.090 | |LOGISTIC REGRESSION| P=0.094 P=0.094 | |COCH-ARM / FISHERS | P=0.093 P=0.087 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 30 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/53 (23%) 0/102 (0%) | |POLY-3 RATE (b) | 12/40.71 0/79.79 | |POLY-3 PERCENT (g) | 29.5% 0.0% | |TERMINAL (d) | 6/25 (24%) 0/42 (0%) | |FIRST INCIDENCE | 645 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001N** P<0.001N** | |POLY 3 | P<0.001N** P<0.001N** | |POLY 1.5 | P<0.001N** P<0.001N** | |POLY 6 | P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P<0.001N** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Metaplasia Bronchiolar | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 77/102 (75%) | |POLY-3 RATE (b) | 2/39.55 77/91.73 | |POLY-3 PERCENT (g) | 5.1% 83.9% | |TERMINAL (d) | 2/25 (8%) 35/42 (83%) | |FIRST INCIDENCE | 731 (T) 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 31 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 8/101 (8%) | |POLY-3 RATE (b) | 0/38.56 8/79.18 | |POLY-3 PERCENT (g) | 0.0% 10.1% | |TERMINAL (d) | 0/25 (0%) 8/42 (19%) | |FIRST INCIDENCE | --- 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.027 * P=0.027 * | |POLY 3 | P=0.061 P=0.036 * | |POLY 1.5 | P=0.062 P=0.037 * | |POLY 6 | P=0.055 P=0.033 * | |LOGISTIC REGRESSION| (e) P=0.027 * | |COCH-ARM / FISHERS | P=0.046 * P=0.034 * | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 25/51 (49%) 46/101 (46%) | |POLY-3 RATE (b) | 25/42.13 46/86.58 | |POLY-3 PERCENT (g) | 59.3% 53.1% | |TERMINAL (d) | 16/25 (64%) 25/42 (60%) | |FIRST INCIDENCE | 366 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.507 P=0.507 | |POLY 3 | P=0.320N P=0.288N | |POLY 1.5 | P=0.326N P=0.295N | |POLY 6 | P=0.355N P=0.326N | |LOGISTIC REGRESSION| P=0.330N P=0.330N | |COCH-ARM / FISHERS | P=0.408N P=0.407N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 32 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 4/101 (4%) | |POLY-3 RATE (b) | 0/38.56 4/80.08 | |POLY-3 PERCENT (g) | 0.0% 5.0% | |TERMINAL (d) | 0/25 (0%) 2/42 (5%) | |FIRST INCIDENCE | --- 581 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.175 P=0.175 | |POLY 3 | P=0.198 P=0.148 | |POLY 1.5 | P=0.197 P=0.148 | |POLY 6 | P=0.192 P=0.144 | |LOGISTIC REGRESSION| P=0.186 P=0.186 | |COCH-ARM / FISHERS | P=0.183 P=0.191 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 3/100 (3%) | |POLY-3 RATE (b) | 1/40.17 3/79.68 | |POLY-3 PERCENT (g) | 2.5% 3.8% | |TERMINAL (d) | 0/25 (0%) 0/42 (0%) | |FIRST INCIDENCE | 469 598 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.570 P=0.570 | |POLY 3 | P=0.529 P=0.499 | |POLY 1.5 | P=0.529 P=0.499 | |POLY 6 | P=0.525 P=0.495 | |LOGISTIC REGRESSION| P=0.509 P=0.509 | |COCH-ARM / FISHERS | P=0.556 P=0.577 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 33 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/2 (50%) 2/14 (14%) | |POLY-3 RATE (b) | 1/2.00 2/10.23 | |POLY-3 PERCENT (g) | 50.0% 19.5% | |TERMINAL (d) | 0/1 (0%) 0/3 (0%) | |FIRST INCIDENCE | 717 578 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.716 P=0.716 | |POLY 3 | P=0.474N P=0.228N | |POLY 1.5 | P=0.459N P=0.198N | |POLY 6 | P=0.500N P=0.282N | |LOGISTIC REGRESSION| P=0.376N P=0.376N | |COCH-ARM / FISHERS | P=0.404N P=0.350N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 2/14 (14%) | |POLY-3 RATE (b) | 0/1.94 2/10.46 | |POLY-3 PERCENT (g) | 0.0% 19.1% | |TERMINAL (d) | 0/1 (0%) 0/3 (0%) | |FIRST INCIDENCE | --- 474 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.417 P=0.417 | |POLY 3 | P=0.546 P=0.341 | |POLY 1.5 | P=0.557 P=0.365 | |POLY 6 | P=0.528 P=0.306 | |LOGISTIC REGRESSION| P=0.996 P=0.996 | |COCH-ARM / FISHERS | P=0.716 P=0.758 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 34 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 3/14 (21%) | |POLY-3 RATE (b) | 0/1.94 3/10.33 | |POLY-3 PERCENT (g) | 0.0% 29.1% | |TERMINAL (d) | 0/1 (0%) 0/3 (0%) | |FIRST INCIDENCE | --- 546 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.280 P=0.280 | |POLY 3 | P=0.487 P=0.249 | |POLY 1.5 | P=0.503 P=0.281 | |POLY 6 | P=0.461 P=0.207 | |LOGISTIC REGRESSION| P=0.639 P=0.639 | |COCH-ARM / FISHERS | P=0.596 P=0.650 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 6/14 (43%) | |POLY-3 RATE (b) | 0/1.94 6/11.11 | |POLY-3 PERCENT (g) | 0.0% 54.0% | |TERMINAL (d) | 0/1 (0%) 1/3 (33%) | |FIRST INCIDENCE | --- 474 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.109 P=0.109 | |POLY 3 | P=0.360 P=0.086 | |POLY 1.5 | P=0.390 P=0.120 | |POLY 6 | P=0.314 P=0.052 | |LOGISTIC REGRESSION| P=0.341 P=0.341 | |COCH-ARM / FISHERS | P=0.348 P=0.375 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 35 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 5/103 (5%) | |POLY-3 RATE (b) | 4/41.40 5/81.19 | |POLY-3 PERCENT (g) | 9.7% 6.2% | |TERMINAL (d) | 0/25 (0%) 3/42 (7%) | |FIRST INCIDENCE | 366 641 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.405N P=0.405N | |POLY 3 | P=0.361N P=0.325N | |POLY 1.5 | P=0.355N P=0.319N | |POLY 6 | P=0.379N P=0.346N | |LOGISTIC REGRESSION| P=0.380N P=0.380N | |COCH-ARM / FISHERS | P=0.374N P=0.363N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 25/53 (47%) 35/103 (34%) | |POLY-3 RATE (b) | 25/44.58 35/84.93 | |POLY-3 PERCENT (g) | 56.1% 41.2% | |TERMINAL (d) | 13/25 (52%) 19/42 (45%) | |FIRST INCIDENCE | 487 410 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.170N P=0.170N | |POLY 3 | P=0.085N P=0.061N | |POLY 1.5 | P=0.076N P=0.053N | |POLY 6 | P=0.117N P=0.091N | |LOGISTIC REGRESSION| P=0.045N* P=0.045N* | |COCH-ARM / FISHERS | P=0.076N P=0.077N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 36 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Mesentery: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 8/9 (89%) | |POLY-3 RATE (b) | 0/0.71 8/8.72 | |POLY-3 PERCENT (g) | 0.0% 91.8% | |TERMINAL (d) | 0/0 (0%) 3/3 (100%) | |FIRST INCIDENCE | --- 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.133 P=0.133 | |POLY 3 | P=0.421 P=0.121 | |POLY 1.5 | P=0.330 P=0.069 | |POLY 6 | P=0.533 P=0.178 | |LOGISTIC REGRESSION| P=0.082 P=0.082 | |COCH-ARM / FISHERS | P=0.047 * P=0.055 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Nose | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 5/103 (5%) | |POLY-3 RATE (b) | 2/40.42 5/81.09 | |POLY-3 PERCENT (g) | 5.0% 6.2% | |TERMINAL (d) | 0/25 (0%) 4/42 (10%) | |FIRST INCIDENCE | 474 638 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.499 P=0.499 | |POLY 3 | P=0.526 P=0.503 | |POLY 1.5 | P=0.527 P=0.504 | |POLY 6 | P=0.515 P=0.490 | |LOGISTIC REGRESSION| P=0.557 P=0.557 | |COCH-ARM / FISHERS | P=0.540 P=0.556 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 37 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Nose: Nasolacrimal Duct | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/103 (1%) | |POLY-3 RATE (b) | 2/40.42 1/81.39 | |POLY-3 PERCENT (g) | 5.0% 1.2% | |TERMINAL (d) | 1/25 (4%) 0/42 (0%) | |FIRST INCIDENCE | 366 520 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.275N P=0.275N | |POLY 3 | P=0.258N P=0.205N | |POLY 1.5 | P=0.258N P=0.205N | |POLY 6 | P=0.261N P=0.209N | |LOGISTIC REGRESSION| P=0.367N P=0.367N | |COCH-ARM / FISHERS | P=0.277N P=0.266N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Nose: Septum | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/103 (2%) | |POLY-3 RATE (b) | 0/39.55 2/81.09 | |POLY-3 PERCENT (g) | 0.0% 2.5% | |TERMINAL (d) | 0/25 (0%) 1/42 (2%) | |FIRST INCIDENCE | --- 638 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.380 P=0.380 | |POLY 3 | P=0.374 P=0.315 | |POLY 1.5 | P=0.372 P=0.314 | |POLY 6 | P=0.371 P=0.312 | |LOGISTIC REGRESSION| P=0.403 P=0.403 | |COCH-ARM / FISHERS | P=0.394 P=0.434 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 38 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Nose: Turbinate, Septum | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/103 (2%) | |POLY-3 RATE (b) | 0/39.55 2/81.64 | |POLY-3 PERCENT (g) | 0.0% 2.5% | |TERMINAL (d) | 0/25 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 561 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.418 P=0.418 | |POLY 3 | P=0.375 P=0.316 | |POLY 1.5 | P=0.373 P=0.314 | |POLY 6 | P=0.373 P=0.314 | |LOGISTIC REGRESSION| P=0.360 P=0.360 | |COCH-ARM / FISHERS | P=0.394 P=0.434 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Oral Mucosa: Gingival | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/2 (50%) 24/40 (60%) | |POLY-3 RATE (b) | 1/1.13 24/34.97 | |POLY-3 PERCENT (g) | 88.9% 68.6% | |TERMINAL (d) | 1/1 (100%) 8/11 (73%) | |FIRST INCIDENCE | 731 (T) 345 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.009 ** P=0.009 ** | |POLY 3 | P=0.543N P=0.377N | |POLY 1.5 | P=0.554N P=0.453N | |POLY 6 | P=0.546N P=0.346N | |LOGISTIC REGRESSION| P=0.780N P=0.780N | |COCH-ARM / FISHERS | P=0.676 P=0.652 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 39 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Ovary | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 49/51 (96%) 76/102 (75%) | |POLY-3 RATE (b) | 49/50.31 76/95.94 | |POLY-3 PERCENT (g) | 97.4% 79.2% | |TERMINAL (d) | 24/25 (96%) 31/42 (74%) | |FIRST INCIDENCE | 169 345 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.142N P=0.142N | |POLY 3 | P=0.003N** P<0.001N** | |POLY 1.5 | P=0.003N** P<0.001N** | |POLY 6 | P=0.005N** P=0.002N** | |LOGISTIC REGRESSION| P<0.001N** P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P<0.001N** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 14/51 (27%) 29/102 (28%) | |POLY-3 RATE (b) | 14/40.42 29/86.11 | |POLY-3 PERCENT (g) | 34.6% 33.7% | |TERMINAL (d) | 10/25 (40%) 12/42 (29%) | |FIRST INCIDENCE | 533 474 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.404 P=0.404 | |POLY 3 | P=0.522N P=0.510N | |POLY 1.5 | P=0.538N P=0.530N | |POLY 6 | P=0.519N P=0.507N | |LOGISTIC REGRESSION| P=0.567 P=0.567 | |COCH-ARM / FISHERS | P=0.525 P=0.529 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 40 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Oviduct | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/2 (100%) 3/3 (100%) | |POLY-3 RATE (b) | 2/2.00 3/3.00 | |POLY-3 PERCENT (g) | 100.0% 100.0% | |TERMINAL (d) | 1/1 (100%) 2/2 (100%) | |FIRST INCIDENCE | 717 643 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) | |POLY 3 | (e) (e) | |POLY 1.5 | (e) (e) | |POLY 6 | (e) (e) | |LOGISTIC REGRESSION| (e) (e) | |COCH-ARM / FISHERS | (e) (e) | |ORDER RESTRICTED | (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pancreas | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 10/100 (10%) | |POLY-3 RATE (b) | 0/38.86 10/80.56 | |POLY-3 PERCENT (g) | 0.0% 12.4% | |TERMINAL (d) | 0/25 (0%) 5/42 (12%) | |FIRST INCIDENCE | --- 581 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.021 * P=0.021 * | |POLY 3 | P=0.036 * P=0.019 * | |POLY 1.5 | P=0.035 * P=0.019 * | |POLY 6 | P=0.034 * P=0.018 * | |LOGISTIC REGRESSION| P=0.025 * P=0.025 * | |COCH-ARM / FISHERS | P=0.023 * P=0.014 * | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 41 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/51 (2%) 13/100 (13%) | |POLY-3 RATE (b) | 1/38.86 13/81.31 | |POLY-3 PERCENT (g) | 2.6% 16.0% | |TERMINAL (d) | 1/25 (4%) 6/42 (14%) | |FIRST INCIDENCE | 731 (T) 581 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.025 * P=0.025 * | |POLY 3 | P=0.045 * P=0.026 * | |POLY 1.5 | P=0.043 * P=0.025 * | |POLY 6 | P=0.044 * P=0.025 * | |LOGISTIC REGRESSION| P=0.030 * P=0.030 * | |COCH-ARM / FISHERS | P=0.028 * P=0.021 * | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/51 (4%) 0/100 (0%) | |POLY-3 RATE (b) | 2/39.17 0/78.62 | |POLY-3 PERCENT (g) | 5.1% 0.0% | |TERMINAL (d) | 1/25 (4%) 0/42 (0%) | |FIRST INCIDENCE | 646 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.129N P=0.129N | |POLY 3 | P=0.105N P=0.064N | |POLY 1.5 | P=0.105N P=0.064N | |POLY 6 | P=0.107N P=0.067N | |LOGISTIC REGRESSION| P=0.103N P=0.103N | |COCH-ARM / FISHERS | P=0.107N P=0.113N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 42 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/51 (2%) 42/100 (42%) | |POLY-3 RATE (b) | 1/39.16 42/84.91 | |POLY-3 PERCENT (g) | 2.6% 49.5% | |TERMINAL (d) | 0/25 (0%) 21/42 (50%) | |FIRST INCIDENCE | 648 546 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pancreas: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 9/100 (9%) | |POLY-3 RATE (b) | 0/38.86 9/80.84 | |POLY-3 PERCENT (g) | 0.0% 11.1% | |TERMINAL (d) | 0/25 (0%) 5/42 (12%) | |FIRST INCIDENCE | --- 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.029 * P=0.029 * | |POLY 3 | P=0.048 * P=0.027 * | |POLY 1.5 | P=0.048 * P=0.027 * | |POLY 6 | P=0.046 * P=0.026 * | |LOGISTIC REGRESSION| P=0.028 * P=0.028 * | |COCH-ARM / FISHERS | P=0.032 * P=0.022 * | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 43 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pituitary Gland | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 25/53 (47%) 24/102 (24%) | |POLY-3 RATE (b) | 25/42.71 24/82.68 | |POLY-3 PERCENT (g) | 58.5% 29.0% | |TERMINAL (d) | 14/25 (56%) 12/42 (29%) | |FIRST INCIDENCE | 474 614 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.011N* P=0.011N* | |POLY 3 | P=0.002N** P<0.001N** | |POLY 1.5 | P=0.002N** P<0.001N** | |POLY 6 | P=0.002N** P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P<0.001N** | |COCH-ARM / FISHERS | P=0.002N** P=0.003N** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pituitary Gland | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 3/102 (3%) | |POLY-3 RATE (b) | 0/39.55 3/80.81 | |POLY-3 PERCENT (g) | 0.0% 3.7% | |TERMINAL (d) | 0/25 (0%) 2/42 (5%) | |FIRST INCIDENCE | --- 673 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.238 P=0.238 | |POLY 3 | P=0.265 P=0.212 | |POLY 1.5 | P=0.263 P=0.210 | |POLY 6 | P=0.261 P=0.208 | |LOGISTIC REGRESSION| P=0.265 P=0.265 | |COCH-ARM / FISHERS | P=0.259 P=0.282 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 44 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 19/53 (36%) 37/102 (36%) | |POLY-3 RATE (b) | 19/43.37 37/87.40 | |POLY-3 PERCENT (g) | 43.8% 42.3% | |TERMINAL (d) | 11/25 (44%) 17/42 (41%) | |FIRST INCIDENCE | 487 578 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.472 P=0.472 | |POLY 3 | P=0.498N P=0.486N | |POLY 1.5 | P=0.507N P=0.496N | |POLY 6 | P=0.507N P=0.495N | |LOGISTIC REGRESSION| P=0.526N P=0.526N | |COCH-ARM / FISHERS | P=0.549 P=0.551 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Intermedia | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/102 (1%) | |POLY-3 RATE (b) | 2/40.18 1/80.59 | |POLY-3 PERCENT (g) | 5.0% 1.2% | |TERMINAL (d) | 1/25 (4%) 1/42 (2%) | |FIRST INCIDENCE | 526 731 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.296N P=0.296N | |POLY 3 | P=0.258N P=0.206N | |POLY 1.5 | P=0.259N P=0.207N | |POLY 6 | P=0.263N P=0.213N | |LOGISTIC REGRESSION| P=0.274N P=0.274N | |COCH-ARM / FISHERS | P=0.280N P=0.269N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 45 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Salivary Glands | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 2/101 (2%) | |POLY-3 RATE (b) | 0/38.56 2/79.29 | |POLY-3 PERCENT (g) | 0.0% 2.5% | |TERMINAL (d) | 0/25 (0%) 1/42 (2%) | |FIRST INCIDENCE | --- 702 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.378 P=0.378 | |POLY 3 | P=0.374 P=0.313 | |POLY 1.5 | P=0.375 P=0.314 | |POLY 6 | P=0.369 P=0.309 | |LOGISTIC REGRESSION| P=0.393 P=0.393 | |COCH-ARM / FISHERS | P=0.398 P=0.440 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Skin | | Cyst Epithelial Inclusion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 2/103 (2%) | |POLY-3 RATE (b) | 1/39.55 2/80.99 | |POLY-3 PERCENT (g) | 2.5% 2.5% | |TERMINAL (d) | 1/25 (4%) 1/42 (2%) | |FIRST INCIDENCE | 731 (T) 668 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.688 P=0.688 | |POLY 3 | P=0.670N P=0.652N | |POLY 1.5 | P=0.671N P=0.654N | |POLY 6 | P=0.674N P=0.657N | |LOGISTIC REGRESSION| P=0.731 P=0.731 | |COCH-ARM / FISHERS | P=0.723 P=0.715N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 46 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 46/51 (90%) 85/101 (84%) | |POLY-3 RATE (b) | 46/47.32 85/95.74 | |POLY-3 PERCENT (g) | 97.2% 88.8% | |TERMINAL (d) | 25/25 (100%) 41/42 (98%) | |FIRST INCIDENCE | 185 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.502 P=0.502 | |POLY 3 | P=0.069N P=0.043N* | |POLY 1.5 | P=0.099N P=0.068N | |POLY 6 | P=0.058N P=0.034N* | |LOGISTIC REGRESSION| P=0.123N P=0.123N | |COCH-ARM / FISHERS | P=0.221N P=0.224N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Spleen | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/51 (2%) 5/101 (5%) | |POLY-3 RATE (b) | 1/39.45 5/80.33 | |POLY-3 PERCENT (g) | 2.5% 6.2% | |TERMINAL (d) | 0/25 (0%) 2/42 (5%) | |FIRST INCIDENCE | 645 641 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.295 P=0.295 | |POLY 3 | P=0.329 P=0.284 | |POLY 1.5 | P=0.331 P=0.286 | |POLY 6 | P=0.321 P=0.276 | |LOGISTIC REGRESSION| P=0.332 P=0.332 | |COCH-ARM / FISHERS | P=0.325 P=0.342 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 47 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 45/51 (88%) 89/101 (88%) | |POLY-3 RATE (b) | 45/49.73 89/95.56 | |POLY-3 PERCENT (g) | 90.5% 93.1% | |TERMINAL (d) | 23/25 (92%) 41/42 (98%) | |FIRST INCIDENCE | 169 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.319 P=0.319 | |POLY 3 | P=0.381 P=0.347 | |POLY 1.5 | P=0.461 P=0.436 | |POLY 6 | P=0.299 P=0.256 | |LOGISTIC REGRESSION| P=0.524N P=0.524N | |COCH-ARM / FISHERS | P=0.597N P=0.604 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/51 (8%) 2/101 (2%) | |POLY-3 RATE (b) | 4/42.10 2/80.28 | |POLY-3 PERCENT (g) | 9.5% 2.5% | |TERMINAL (d) | 0/25 (0%) 0/42 (0%) | |FIRST INCIDENCE | 169 520 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.095N P=0.095N | |POLY 3 | P=0.111N P=0.077N | |POLY 1.5 | P=0.108N P=0.074N | |POLY 6 | P=0.118N P=0.084N | |LOGISTIC REGRESSION| P=0.204N P=0.204N | |COCH-ARM / FISHERS | P=0.095N P=0.098N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 48 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 4/103 (4%) | |POLY-3 RATE (b) | 1/40.16 4/82.30 | |POLY-3 PERCENT (g) | 2.5% 4.9% | |TERMINAL (d) | 0/25 (0%) 1/42 (2%) | |FIRST INCIDENCE | 533 520 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.447 P=0.447 | |POLY 3 | P=0.424 P=0.384 | |POLY 1.5 | P=0.422 P=0.382 | |POLY 6 | P=0.418 P=0.379 | |LOGISTIC REGRESSION| P=0.365 P=0.365 | |COCH-ARM / FISHERS | P=0.424 P=0.446 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 16/103 (16%) | |POLY-3 RATE (b) | 3/39.67 16/85.58 | |POLY-3 PERCENT (g) | 7.6% 18.7% | |TERMINAL (d) | 2/25 (8%) 4/42 (10%) | |FIRST INCIDENCE | 701 474 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.068 P=0.068 | |POLY 3 | P=0.109 P=0.077 | |POLY 1.5 | P=0.100 P=0.070 | |POLY 6 | P=0.115 P=0.081 | |LOGISTIC REGRESSION| P=0.062 P=0.062 | |COCH-ARM / FISHERS | P=0.063 P=0.058 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 49 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 9/103 (9%) | |POLY-3 RATE (b) | 1/40.42 9/84.35 | |POLY-3 PERCENT (g) | 2.5% 10.7% | |TERMINAL (d) | 0/25 (0%) 1/42 (2%) | |FIRST INCIDENCE | 366 474 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.112 P=0.112 | |POLY 3 | P=0.127 P=0.091 | |POLY 1.5 | P=0.123 P=0.088 | |POLY 6 | P=0.127 P=0.091 | |LOGISTIC REGRESSION| P=0.054 P=0.054 | |COCH-ARM / FISHERS | P=0.095 P=0.089 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 8/103 (8%) | |POLY-3 RATE (b) | 2/40.54 8/84.00 | |POLY-3 PERCENT (g) | 4.9% 9.5% | |TERMINAL (d) | 0/25 (0%) 1/42 (2%) | |FIRST INCIDENCE | 366 474 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.285 P=0.285 | |POLY 3 | P=0.301 P=0.260 | |POLY 1.5 | P=0.295 P=0.255 | |POLY 6 | P=0.299 P=0.258 | |LOGISTIC REGRESSION| P=0.190 P=0.190 | |COCH-ARM / FISHERS | P=0.268 P=0.276 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 50 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Stomach, Glandular | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 0/103 (0%) | |POLY-3 RATE (b) | 3/41.09 0/80.75 | |POLY-3 PERCENT (g) | 7.3% 0.0% | |TERMINAL (d) | 0/25 (0%) 0/42 (0%) | |FIRST INCIDENCE | 169 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.039N* P=0.039N* | |POLY 3 | P=0.038N* P=0.019N* | |POLY 1.5 | P=0.038N* P=0.019N* | |POLY 6 | P=0.039N* P=0.021N* | |LOGISTIC REGRESSION| P=0.069N P=0.069N | |COCH-ARM / FISHERS | P=0.034N* P=0.038N* | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Stomach, Glandular | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/103 (2%) | |POLY-3 RATE (b) | 0/39.55 2/81.34 | |POLY-3 PERCENT (g) | 0.0% 2.5% | |TERMINAL (d) | 0/25 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 604 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.399 P=0.399 | |POLY 3 | P=0.375 P=0.315 | |POLY 1.5 | P=0.373 P=0.314 | |POLY 6 | P=0.372 P=0.313 | |LOGISTIC REGRESSION| P=0.391 P=0.391 | |COCH-ARM / FISHERS | P=0.394 P=0.434 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 51 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 36/51 (71%) 87/91 (96%) | |POLY-3 RATE (b) | 36/45.37 87/88.27 | |POLY-3 PERCENT (g) | 79.3% 98.6% | |TERMINAL (d) | 20/25 (80%) 39/39 (100%) | |FIRST INCIDENCE | 169 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.020 * P=0.020 * | |POLY 3 | P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 19/52 (37%) 38/101 (38%) | |POLY-3 RATE (b) | 19/40.39 38/87.81 | |POLY-3 PERCENT (g) | 47.0% 43.3% | |TERMINAL (d) | 12/25 (48%) 15/42 (36%) | |FIRST INCIDENCE | 646 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.420 P=0.420 | |POLY 3 | P=0.416N P=0.392N | |POLY 1.5 | P=0.466N P=0.449N | |POLY 6 | P=0.392N P=0.366N | |LOGISTIC REGRESSION| P=0.558N P=0.558N | |COCH-ARM / FISHERS | P=0.518 P=0.520 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 52 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 0/101 (0%) | |POLY-3 RATE (b) | 2/38.90 0/79.18 | |POLY-3 PERCENT (g) | 5.1% 0.0% | |TERMINAL (d) | 2/25 (8%) 0/42 (0%) | |FIRST INCIDENCE | 731 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.133N P=0.133N | |POLY 3 | P=0.104N P=0.063N | |POLY 1.5 | P=0.104N P=0.064N | |POLY 6 | P=0.105N P=0.065N | |LOGISTIC REGRESSION| P=0.133N (e) | |COCH-ARM / FISHERS | P=0.109N P=0.114N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/52 (6%) 23/101 (23%) | |POLY-3 RATE (b) | 3/39.78 23/83.83 | |POLY-3 PERCENT (g) | 7.5% 27.4% | |TERMINAL (d) | 2/25 (8%) 12/42 (29%) | |FIRST INCIDENCE | 361 396 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.007 ** P=0.007 ** | |POLY 3 | P=0.017 * P=0.008 ** | |POLY 1.5 | P=0.016 * P=0.007 ** | |POLY 6 | P=0.016 * P=0.008 ** | |LOGISTIC REGRESSION| P=0.008 ** P=0.008 ** | |COCH-ARM / FISHERS | P=0.008 ** P=0.005 ** | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 53 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Tooth: Peridontal Tissue | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/16 (94%) 30/30 (100%) | |POLY-3 RATE (b) | 15/15.64 30/30.00 | |POLY-3 PERCENT (g) | 95.9% 100.0% | |TERMINAL (d) | 9/9 (100%) 13/13 (100%) | |FIRST INCIDENCE | 185 345 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.292 P=0.292 | |POLY 3 | P=0.494 P=0.400 | |POLY 1.5 | P=0.399 P=0.319 | |POLY 6 | P=0.745 P=0.639 | |LOGISTIC REGRESSION| P=0.374 P=0.374 | |COCH-ARM / FISHERS | P=0.373 P=0.348 | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Urinary Bladder | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/52 (12%) 5/103 (5%) | |POLY-3 RATE (b) | 6/39.16 5/81.24 | |POLY-3 PERCENT (g) | 15.3% 6.2% | |TERMINAL (d) | 4/25 (16%) 2/42 (5%) | |FIRST INCIDENCE | 697 645 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.162N P=0.162N | |POLY 3 | P=0.114N P=0.079N | |POLY 1.5 | P=0.116N P=0.081N | |POLY 6 | P=0.117N P=0.083N | |LOGISTIC REGRESSION| P=0.112N P=0.112N | |COCH-ARM / FISHERS | P=0.115N P=0.117N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 54 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Urinary Bladder: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 2/103 (2%) | |POLY-3 RATE (b) | 1/38.97 2/80.87 | |POLY-3 PERCENT (g) | 2.6% 2.5% | |TERMINAL (d) | 1/25 (4%) 1/42 (2%) | |FIRST INCIDENCE | 731 (T) 701 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.693 P=0.693 | |POLY 3 | P=0.666N P=0.647N | |POLY 1.5 | P=0.666N P=0.648N | |POLY 6 | P=0.672N P=0.654N | |LOGISTIC REGRESSION| P=0.722 P=0.722 | |COCH-ARM / FISHERS | P=0.729 P=0.709N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Uterus | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/52 (13%) 14/103 (14%) | |POLY-3 RATE (b) | 7/40.38 14/84.16 | |POLY-3 PERCENT (g) | 17.3% 16.6% | |TERMINAL (d) | 4/25 (16%) 5/42 (12%) | |FIRST INCIDENCE | 185 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.521 P=0.521 | |POLY 3 | P=0.540N P=0.528N | |POLY 1.5 | P=0.549N P=0.538N | |POLY 6 | P=0.545N P=0.533N | |LOGISTIC REGRESSION| P=0.586 P=0.586 | |COCH-ARM / FISHERS | P=0.589 P=0.599N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| Date: 11/25/02 EXPERIMENT: 96007 TEST: 03 Page 55 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Uterus | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 29/52 (56%) 50/103 (49%) | |POLY-3 RATE (b) | 29/45.30 50/91.58 | |POLY-3 PERCENT (g) | 64.0% 54.6% | |TERMINAL (d) | 15/25 (60%) 23/42 (55%) | |FIRST INCIDENCE | 351 394 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.424N P=0.424N | |POLY 3 | P=0.204N P=0.169N | |POLY 1.5 | P=0.211N P=0.176N | |POLY 6 | P=0.211N P=0.176N | |LOGISTIC REGRESSION| P=0.223N P=0.223N | |COCH-ARM / FISHERS | P=0.248N P=0.249N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 100 | | | NG/KG | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 30/52 (58%) 51/103 (50%) | |POLY-3 RATE (b) | 30/44.70 51/87.17 | |POLY-3 PERCENT (g) | 67.1% 58.5% | |TERMINAL (d) | 15/25 (60%) 28/42 (67%) | |FIRST INCIDENCE | 361 474 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.432N P=0.432N | |POLY 3 | P=0.223N P=0.189N | |POLY 1.5 | P=0.198N P=0.164N | |POLY 6 | P=0.306N P=0.276N | |LOGISTIC REGRESSION| P=0.128N P=0.128N | |COCH-ARM / FISHERS | P=0.214N P=0.214N | |ORDER RESTRICTED | P<0.001 ** (e) | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Number of tumor-bearing animals / Poly-3 number (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers exact tests compare directly the overall incidence rates For all tests a negative trend is indicated by N (e) Value of Statistic cannot be computed. (g) Poly-3 adjusted lifetime tumor incidence. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).