TDMS Study 96007-05 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) DATE: 09/30/03 EXPERIMENT: 96007 TEST: 05 TIME: 11:38:42 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007F PATHOLOGIST: SELLS, DONALD CAS: 57117-31-4 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #3/CONTROL VS. STOP GROUPS 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 007 200 NG/ KG STOP NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) DATE: 09/30/03 EXPERIMENT: 96007 TEST: 05 TIME: 11:38:42 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007F PATHOLOGIST: SELLS, DONALD CAS: 57117-31-4 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 Clitoral Gland Inflammation Clitoral Gland: Duct Cyst Harderian Gland Inflammation Heart Cardiomyopathy Hemorrhage Intestine Large, Colon Parasite Metazoan Intestine Large, Rectum Parasite Metazoan Kidney Accumulation, Hyaline Droplet Calculus Micro Observation Only Inflammation Mineralization Nephropathy Pigmentation Kidney: Transitional Epithelium Hyperplasia Liver Angiectasis Basophilic Focus Cholangiofibrosis Clear Cell Focus Eosinophilic Focus Fatty Change Diffuse Fatty Change Focal Hematopoietic Cell Proliferation Hepatodiaphragmatic Nodule Inflammation Mixed Cell Focus Necrosis Pigmentation Toxic Hepatopathy Liver: Bile Duct Cyst Hyperplasia Liver: Centrilobular Degeneration Liver: Hepatocyte Hypertrophy Multinucleated Liver: Oval Cell Hyperplasia Lung Hemorrhage Infiltration Cellular Histiocyte Inflammation Lung: Alveolar Epithelium Hyperplasia Metaplasia Bronchiolar NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF) DATE: 09/30/03 EXPERIMENT: 96007 TEST: 05 TIME: 11:38:42 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-75411 ROUTE: GAVAGE NTP C#: 96007F PATHOLOGIST: SELLS, DONALD CAS: 57117-31-4 Lymph Node, Mandibular Hyperplasia Lymph Node: Lumbar Ectasia Hemorrhage Mammary Gland Cyst Hyperplasia Inflammation Granulomatous Nose Inflammation Nose: Respiratory Epithelium Hyperplasia Oral Mucosa: Gingival Hyperplasia Ovary Atrophy Cyst Pancreas Inflammation Chronic Pancreas: Acinus Atrophy Vacuolization Cytoplasmic Pituitary Gland Angiectasis Cyst Cytoplasmic Alteration Vacuolization Cytoplasmic Pituitary Gland: Pars Distalis Hyperplasia Skin Inflammation Ulcer Spleen Hematopoietic Cell Proliferation Pigmentation Spleen: Lymphoid Follicle Atrophy Spleen: Red Pulp Atrophy Stomach, Forestomach Hyperplasia Stomach, Glandular Mineralization Thymus Atrophy Thyroid Gland: C-Cell Hyperplasia Thyroid Gland: Follicular Cell Hypertrophy Urinary Bladder Inflammation Urinary Bladder: Transitional Epithelium Hyperplasia Uterus Inflammation Inflammation Chronic Metaplasia Uterus: Endometrium Hyperplasia Cystic =============================================================== Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Adrenal Cortex | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 31/53 (58%) 29/48 (60%) | |POLY-3 RATE (b) | 31/44.10 29/40.00 | |POLY-3 PERCENT (g) | 70.3% 72.5% | |TERMINAL (d) | 20/25 (80%) 13/15 (87%) | |FIRST INCIDENCE | 588 276 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.045 * | |POLY 3 | P=0.513 | |POLY 1.5 | P=0.518 | |POLY 6 | P=0.498 | |LOGISTIC REGRESSION| P=0.251 | |COCH-ARM / FISHERS | P=0.503 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Adrenal Cortex | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 0/48 (0%) | |POLY-3 RATE (b) | 3/42.22 0/32.61 | |POLY-3 PERCENT (g) | 7.1% 0.0% | |TERMINAL (d) | 1/25 (4%) 0/15 (0%) | |FIRST INCIDENCE | 619 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.207N | |POLY 3 | P=0.194N | |POLY 1.5 | P=0.171N | |POLY 6 | P=0.223N | |LOGISTIC REGRESSION| P=0.166N | |COCH-ARM / FISHERS | P=0.141N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Adrenal Cortex | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 12/48 (25%) | |POLY-3 RATE (b) | 4/42.40 12/35.26 | |POLY-3 PERCENT (g) | 9.4% 34.0% | |TERMINAL (d) | 2/25 (8%) 7/15 (47%) | |FIRST INCIDENCE | 603 240 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** | |POLY 3 | P=0.007 ** | |POLY 1.5 | P=0.010 * | |POLY 6 | P=0.004 ** | |LOGISTIC REGRESSION| P=0.013 * | |COCH-ARM / FISHERS | P=0.016 * | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/53 (15%) 7/48 (15%) | |POLY-3 RATE (b) | 8/42.51 7/35.22 | |POLY-3 PERCENT (g) | 18.8% 19.9% | |TERMINAL (d) | 6/25 (24%) 2/15 (13%) | |FIRST INCIDENCE | 588 370 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.393 | |POLY 3 | P=0.580 | |POLY 1.5 | P=0.604 | |POLY 6 | P=0.555 | |LOGISTIC REGRESSION| P=0.598 | |COCH-ARM / FISHERS | P=0.583N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 42/53 (79%) 36/48 (75%) | |POLY-3 RATE (b) | 42/48.81 36/41.10 | |POLY-3 PERCENT (g) | 86.1% 87.6% | |TERMINAL (d) | 23/25 (92%) 14/15 (93%) | |FIRST INCIDENCE | 377 240 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.095 | |POLY 3 | P=0.557 | |POLY 1.5 | P=0.577N | |POLY 6 | P=0.396 | |LOGISTIC REGRESSION| P=0.571 | |COCH-ARM / FISHERS | P=0.393N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Adrenal Cortex | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 3/48 (6%) | |POLY-3 RATE (b) | 4/43.02 3/33.19 | |POLY-3 PERCENT (g) | 9.3% 9.0% | |TERMINAL (d) | 0/25 (0%) 0/15 (0%) | |FIRST INCIDENCE | 500 605 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.608 | |POLY 3 | P=0.661N | |POLY 1.5 | P=0.622N | |POLY 6 | P=0.663 | |LOGISTIC REGRESSION| P=0.575N | |COCH-ARM / FISHERS | P=0.556N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Adrenal Cortex | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/53 (17%) 10/48 (21%) | |POLY-3 RATE (b) | 9/42.91 10/33.82 | |POLY-3 PERCENT (g) | 21.0% 29.6% | |TERMINAL (d) | 5/25 (20%) 6/15 (40%) | |FIRST INCIDENCE | 536 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.147 | |POLY 3 | P=0.286 | |POLY 1.5 | P=0.334 | |POLY 6 | P=0.237 | |LOGISTIC REGRESSION| P=0.252 | |COCH-ARM / FISHERS | P=0.405 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/53 (21%) 7/48 (15%) | |POLY-3 RATE (b) | 11/42.90 7/35.03 | |POLY-3 PERCENT (g) | 25.6% 20.0% | |TERMINAL (d) | 7/25 (28%) 3/15 (20%) | |FIRST INCIDENCE | 500 370 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.570N | |POLY 3 | P=0.386N | |POLY 1.5 | P=0.348N | |POLY 6 | P=0.430N | |LOGISTIC REGRESSION| P=0.344N | |COCH-ARM / FISHERS | P=0.293N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 38/53 (72%) 43/50 (86%) | |POLY-3 RATE (b) | 38/52.51 43/49.89 | |POLY-3 PERCENT (g) | 72.4% 86.2% | |TERMINAL (d) | 12/25 (48%) 9/15 (60%) | |FIRST INCIDENCE | 289 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.017 * | |POLY 3 | P=0.068 | |POLY 1.5 | P=0.065 | |POLY 6 | P=0.072 | |LOGISTIC REGRESSION| P=0.223 | |COCH-ARM / FISHERS | P=0.062 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 52/53 (98%) 48/50 (96%) | |POLY-3 RATE (b) | 52/52.72 48/49.33 | |POLY-3 PERCENT (g) | 98.6% 97.3% | |TERMINAL (d) | 25/25 (100%) 14/15 (93%) | |FIRST INCIDENCE | 289 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.043 * | |POLY 3 | P=0.609N | |POLY 1.5 | P=0.563N | |POLY 6 | P=0.634N | |LOGISTIC REGRESSION| P=0.482N | |COCH-ARM / FISHERS | P=0.478N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Clitoral Gland: Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 40/53 (75%) 39/50 (78%) | |POLY-3 RATE (b) | 40/50.78 39/44.51 | |POLY-3 PERCENT (g) | 78.8% 87.6% | |TERMINAL (d) | 18/25 (72%) 12/15 (80%) | |FIRST INCIDENCE | 289 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.045 * | |POLY 3 | P=0.183 | |POLY 1.5 | P=0.264 | |POLY 6 | P=0.134 | |LOGISTIC REGRESSION| P=0.401 | |COCH-ARM / FISHERS | P=0.473 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Harderian Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 16/53 (30%) 6/49 (12%) | |POLY-3 RATE (b) | 16/42.80 6/34.36 | |POLY-3 PERCENT (g) | 37.4% 17.5% | |TERMINAL (d) | 11/25 (44%) 2/15 (13%) | |FIRST INCIDENCE | 610 500 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.154N | |POLY 3 | P=0.046N* | |POLY 1.5 | P=0.036N* | |POLY 6 | P=0.060N | |LOGISTIC REGRESSION| P=0.061N | |COCH-ARM / FISHERS | P=0.024N* | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/53 (28%) 13/50 (26%) | |POLY-3 RATE (b) | 15/43.14 13/35.36 | |POLY-3 PERCENT (g) | 34.8% 36.8% | |TERMINAL (d) | 9/25 (36%) 5/15 (33%) | |FIRST INCIDENCE | 500 503 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.261 | |POLY 3 | P=0.533 | |POLY 1.5 | P=0.591 | |POLY 6 | P=0.478 | |LOGISTIC REGRESSION| P=0.465 | |COCH-ARM / FISHERS | P=0.484N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Heart | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 2/43.24 0/32.95 | |POLY-3 PERCENT (g) | 4.6% 0.0% | |TERMINAL (d) | 0/25 (0%) 0/15 (0%) | |FIRST INCIDENCE | 377 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.283N | |POLY 3 | P=0.345N | |POLY 1.5 | P=0.308N | |POLY 6 | P=0.388N | |LOGISTIC REGRESSION| P=0.149N | |COCH-ARM / FISHERS | P=0.262N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Intestine Large, Colon | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/49 (0%) | |POLY-3 RATE (b) | 2/42.66 0/32.31 | |POLY-3 PERCENT (g) | 4.7% 0.0% | |TERMINAL (d) | 0/25 (0%) 0/15 (0%) | |FIRST INCIDENCE | 536 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.320N | |POLY 3 | P=0.346N | |POLY 1.5 | P=0.312N | |POLY 6 | P=0.388N | |LOGISTIC REGRESSION| P=0.227N | |COCH-ARM / FISHERS | P=0.268N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Intestine Large, Rectum | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 2/50 (4%) | |POLY-3 RATE (b) | 4/41.97 2/32.95 | |POLY-3 PERCENT (g) | 9.5% 6.1% | |TERMINAL (d) | 3/25 (12%) 2/15 (13%) | |FIRST INCIDENCE | 678 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.574N | |POLY 3 | P=0.478N | |POLY 1.5 | P=0.434N | |POLY 6 | P=0.528N | |LOGISTIC REGRESSION| P=0.527N | |COCH-ARM / FISHERS | P=0.367N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Kidney | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 3/48 (6%) | |POLY-3 RATE (b) | 0/41.78 3/33.51 | |POLY-3 PERCENT (g) | 0.0% 9.0% | |TERMINAL (d) | 0/25 (0%) 1/15 (7%) | |FIRST INCIDENCE | --- 384 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.072 | |POLY 3 | P=0.094 | |POLY 1.5 | P=0.099 | |POLY 6 | P=0.090 | |LOGISTIC REGRESSION| P=0.111 | |COCH-ARM / FISHERS | P=0.104 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Kidney | | Calculus Micro Observation Only | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 1/48 (2%) | |POLY-3 RATE (b) | 5/41.89 1/33.46 | |POLY-3 PERCENT (g) | 11.9% 3.0% | |TERMINAL (d) | 4/25 (16%) 0/15 (0%) | |FIRST INCIDENCE | 699 384 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.221N | |POLY 3 | P=0.173N | |POLY 1.5 | P=0.154N | |POLY 6 | P=0.198N | |LOGISTIC REGRESSION| P=0.146N | |COCH-ARM / FISHERS | P=0.127N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Kidney | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 3/48 (6%) | |POLY-3 RATE (b) | 2/42.16 3/32.66 | |POLY-3 PERCENT (g) | 4.7% 9.2% | |TERMINAL (d) | 1/25 (4%) 2/15 (13%) | |FIRST INCIDENCE | 619 715 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.302 | |POLY 3 | P=0.411 | |POLY 1.5 | P=0.432 | |POLY 6 | P=0.389 | |LOGISTIC REGRESSION| P=0.357 | |COCH-ARM / FISHERS | P=0.453 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 37/53 (70%) 41/48 (85%) | |POLY-3 RATE (b) | 37/49.64 41/44.94 | |POLY-3 PERCENT (g) | 74.5% 91.2% | |TERMINAL (d) | 20/25 (80%) 13/15 (87%) | |FIRST INCIDENCE | 289 276 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.006 ** | |POLY 3 | P=0.023 * | |POLY 1.5 | P=0.027 * | |POLY 6 | P=0.026 * | |LOGISTIC REGRESSION| P=0.045 * | |COCH-ARM / FISHERS | P=0.051 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 34/53 (64%) 35/48 (73%) | |POLY-3 RATE (b) | 34/45.99 35/41.66 | |POLY-3 PERCENT (g) | 73.9% 84.0% | |TERMINAL (d) | 20/25 (80%) 15/15 (100%) | |FIRST INCIDENCE | 377 240 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.011 * | |POLY 3 | P=0.164 | |POLY 1.5 | P=0.204 | |POLY 6 | P=0.118 | |LOGISTIC REGRESSION| P=0.101 | |COCH-ARM / FISHERS | P=0.233 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Kidney | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/48 (0%) | |POLY-3 RATE (b) | 2/42.16 0/32.61 | |POLY-3 PERCENT (g) | 4.7% 0.0% | |TERMINAL (d) | 1/25 (4%) 0/15 (0%) | |FIRST INCIDENCE | 619 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.334N | |POLY 3 | P=0.336N | |POLY 1.5 | P=0.308N | |POLY 6 | P=0.371N | |LOGISTIC REGRESSION| P=0.282N | |COCH-ARM / FISHERS | P=0.273N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Kidney: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 3/48 (6%) | |POLY-3 RATE (b) | 2/41.78 3/33.23 | |POLY-3 PERCENT (g) | 4.8% 9.0% | |TERMINAL (d) | 2/25 (8%) 2/15 (13%) | |FIRST INCIDENCE | 728 (T) 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.295 | |POLY 3 | P=0.420 | |POLY 1.5 | P=0.437 | |POLY 6 | P=0.402 | |LOGISTIC REGRESSION| P=0.384 | |COCH-ARM / FISHERS | P=0.453 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/53 (11%) 1/50 (2%) | |POLY-3 RATE (b) | 6/42.92 1/33.52 | |POLY-3 PERCENT (g) | 14.0% 3.0% | |TERMINAL (d) | 1/25 (4%) 0/15 (0%) | |FIRST INCIDENCE | 610 547 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.149N | |POLY 3 | P=0.117N | |POLY 1.5 | P=0.095N | |POLY 6 | P=0.148N | |LOGISTIC REGRESSION| P=0.081N | |COCH-ARM / FISHERS | P=0.066N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 22/53 (42%) 13/50 (26%) | |POLY-3 RATE (b) | 22/44.73 13/36.12 | |POLY-3 PERCENT (g) | 49.2% 36.0% | |TERMINAL (d) | 10/25 (40%) 5/15 (33%) | |FIRST INCIDENCE | 513 451 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.431N | |POLY 3 | P=0.169N | |POLY 1.5 | P=0.122N | |POLY 6 | P=0.242N | |LOGISTIC REGRESSION| P=0.158N | |COCH-ARM / FISHERS | P=0.073N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Cholangiofibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 3/50 (6%) | |POLY-3 RATE (b) | 0/41.78 3/33.14 | |POLY-3 PERCENT (g) | 0.0% 9.1% | |TERMINAL (d) | 0/25 (0%) 1/15 (7%) | |FIRST INCIDENCE | --- 692 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.060 | |POLY 3 | P=0.095 | |POLY 1.5 | P=0.100 | |POLY 6 | P=0.090 | |LOGISTIC REGRESSION| P=0.065 | |COCH-ARM / FISHERS | P=0.111 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 13/53 (25%) 6/50 (12%) | |POLY-3 RATE (b) | 13/43.13 6/32.95 | |POLY-3 PERCENT (g) | 30.1% 18.2% | |TERMINAL (d) | 9/25 (36%) 6/15 (40%) | |FIRST INCIDENCE | 321 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.322N | |POLY 3 | P=0.188N | |POLY 1.5 | P=0.140N | |POLY 6 | P=0.257N | |LOGISTIC REGRESSION| P=0.196N | |COCH-ARM / FISHERS | P=0.082N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/53 (28%) 22/50 (44%) | |POLY-3 RATE (b) | 15/45.03 22/38.92 | |POLY-3 PERCENT (g) | 33.3% 56.5% | |TERMINAL (d) | 6/25 (24%) 6/15 (40%) | |FIRST INCIDENCE | 289 370 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.013 * | |POLY 3 | P=0.024 * | |POLY 1.5 | P=0.034 * | |POLY 6 | P=0.019 * | |LOGISTIC REGRESSION| P=0.048 * | |COCH-ARM / FISHERS | P=0.073 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Fatty Change Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 6/50 (12%) | |POLY-3 RATE (b) | 1/41.78 6/34.86 | |POLY-3 PERCENT (g) | 2.4% 17.2% | |TERMINAL (d) | 1/25 (4%) 3/15 (20%) | |FIRST INCIDENCE | 728 (T) 413 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.019 * | |POLY 3 | P=0.033 * | |POLY 1.5 | P=0.038 * | |POLY 6 | P=0.029 * | |LOGISTIC REGRESSION| P=0.046 * | |COCH-ARM / FISHERS | P=0.048 * | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Fatty Change Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 7/50 (14%) | |POLY-3 RATE (b) | 5/42.06 7/34.54 | |POLY-3 PERCENT (g) | 11.9% 20.3% | |TERMINAL (d) | 4/25 (16%) 2/15 (13%) | |FIRST INCIDENCE | 651 476 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.140 | |POLY 3 | P=0.257 | |POLY 1.5 | P=0.287 | |POLY 6 | P=0.231 | |LOGISTIC REGRESSION| P=0.233 | |COCH-ARM / FISHERS | P=0.339 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 24/53 (45%) 31/50 (62%) | |POLY-3 RATE (b) | 24/48.52 31/42.24 | |POLY-3 PERCENT (g) | 49.5% 73.4% | |TERMINAL (d) | 10/25 (40%) 10/15 (67%) | |FIRST INCIDENCE | 289 240 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.008 ** | |POLY 3 | P=0.014 * | |POLY 1.5 | P=0.024 * | |POLY 6 | P=0.008 ** | |LOGISTIC REGRESSION| P=0.072 | |COCH-ARM / FISHERS | P=0.066 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 1/50 (2%) | |POLY-3 RATE (b) | 3/41.97 1/32.95 | |POLY-3 PERCENT (g) | 7.2% 3.0% | |TERMINAL (d) | 2/25 (8%) 1/15 (7%) | |FIRST INCIDENCE | 678 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.484N | |POLY 3 | P=0.425N | |POLY 1.5 | P=0.387N | |POLY 6 | P=0.469N | |LOGISTIC REGRESSION| P=0.443N | |COCH-ARM / FISHERS | P=0.331N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 47/53 (89%) 48/50 (96%) | |POLY-3 RATE (b) | 47/51.32 48/48.98 | |POLY-3 PERCENT (g) | 91.6% 98.0% | |TERMINAL (d) | 23/25 (92%) 15/15 (100%) | |FIRST INCIDENCE | 289 240 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.010 * | |POLY 3 | P=0.145 | |POLY 1.5 | P=0.123 | |POLY 6 | P=0.194 | |LOGISTIC REGRESSION| P=0.112 | |COCH-ARM / FISHERS | P=0.154 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 33/53 (62%) 24/50 (48%) | |POLY-3 RATE (b) | 33/45.39 24/36.74 | |POLY-3 PERCENT (g) | 72.7% 65.3% | |TERMINAL (d) | 21/25 (84%) 11/15 (73%) | |FIRST INCIDENCE | 500 451 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.352 | |POLY 3 | P=0.312N | |POLY 1.5 | P=0.206N | |POLY 6 | P=0.457N | |LOGISTIC REGRESSION| P=0.406N | |COCH-ARM / FISHERS | P=0.104N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 11/50 (22%) | |POLY-3 RATE (b) | 4/44.47 11/39.94 | |POLY-3 PERCENT (g) | 9.0% 27.5% | |TERMINAL (d) | 0/25 (0%) 0/15 (0%) | |FIRST INCIDENCE | 377 240 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.027 * | |POLY 3 | P=0.024 * | |POLY 1.5 | P=0.028 * | |POLY 6 | P=0.021 * | |LOGISTIC REGRESSION| P=0.120 | |COCH-ARM / FISHERS | P=0.035 * | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 13/53 (25%) 48/50 (96%) | |POLY-3 RATE (b) | 13/43.77 48/48.40 | |POLY-3 PERCENT (g) | 29.7% 99.2% | |TERMINAL (d) | 7/25 (28%) 15/15 (100%) | |FIRST INCIDENCE | 321 240 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** | |POLY 3 | P<0.001 ** | |POLY 1.5 | P<0.001 ** | |POLY 6 | P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver | | Toxic Hepatopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 9/50 (18%) | |POLY-3 RATE (b) | 0/41.78 9/33.65 | |POLY-3 PERCENT (g) | 0.0% 26.7% | |TERMINAL (d) | 0/25 (0%) 5/15 (33%) | |FIRST INCIDENCE | --- 610 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** | |POLY 3 | P<0.001 ** | |POLY 1.5 | P<0.001 ** | |POLY 6 | P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver: Bile Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/53 (13%) 2/50 (4%) | |POLY-3 RATE (b) | 7/42.31 2/33.05 | |POLY-3 PERCENT (g) | 16.6% 6.1% | |TERMINAL (d) | 4/25 (16%) 1/15 (7%) | |FIRST INCIDENCE | 651 701 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.242N | |POLY 3 | P=0.164N | |POLY 1.5 | P=0.134N | |POLY 6 | P=0.203N | |LOGISTIC REGRESSION| P=0.182N | |COCH-ARM / FISHERS | P=0.095N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 1/50 (2%) | |POLY-3 RATE (b) | 3/42.17 1/32.95 | |POLY-3 PERCENT (g) | 7.1% 3.0% | |TERMINAL (d) | 1/25 (4%) 1/15 (7%) | |FIRST INCIDENCE | 619 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.484N | |POLY 3 | P=0.427N | |POLY 1.5 | P=0.388N | |POLY 6 | P=0.473N | |LOGISTIC REGRESSION| P=0.416N | |COCH-ARM / FISHERS | P=0.331N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver: Centrilobular | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 7/50 (14%) | |POLY-3 RATE (b) | 4/43.64 7/36.67 | |POLY-3 PERCENT (g) | 9.2% 19.1% | |TERMINAL (d) | 0/25 (0%) 2/15 (13%) | |FIRST INCIDENCE | 310 240 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.145 | |POLY 3 | P=0.175 | |POLY 1.5 | P=0.196 | |POLY 6 | P=0.154 | |LOGISTIC REGRESSION| P=0.388 | |COCH-ARM / FISHERS | P=0.230 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 14/50 (28%) | |POLY-3 RATE (b) | 2/42.11 14/38.76 | |POLY-3 PERCENT (g) | 4.8% 36.1% | |TERMINAL (d) | 0/25 (0%) 3/15 (20%) | |FIRST INCIDENCE | 651 240 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** | |POLY 3 | P<0.001 ** | |POLY 1.5 | P<0.001 ** | |POLY 6 | P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver: Hepatocyte | | Multinucleated | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 25/50 (50%) | |POLY-3 RATE (b) | 0/41.78 25/42.04 | |POLY-3 PERCENT (g) | 0.0% 59.5% | |TERMINAL (d) | 0/25 (0%) 7/15 (47%) | |FIRST INCIDENCE | --- 276 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** | |POLY 3 | P<0.001 ** | |POLY 1.5 | P<0.001 ** | |POLY 6 | P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Liver: Oval Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 3/50 (6%) | |POLY-3 RATE (b) | 1/41.78 3/33.20 | |POLY-3 PERCENT (g) | 2.4% 9.0% | |TERMINAL (d) | 1/25 (4%) 1/15 (7%) | |FIRST INCIDENCE | 728 (T) 689 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.175 | |POLY 3 | P=0.249 | |POLY 1.5 | P=0.263 | |POLY 6 | P=0.236 | |LOGISTIC REGRESSION| P=0.188 | |COCH-ARM / FISHERS | P=0.287 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Lung | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/41.78 2/34.31 | |POLY-3 PERCENT (g) | 0.0% 5.8% | |TERMINAL (d) | 0/25 (0%) 0/15 (0%) | |FIRST INCIDENCE | --- 495 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.194 | |POLY 3 | P=0.218 | |POLY 1.5 | P=0.222 | |POLY 6 | P=0.215 | |LOGISTIC REGRESSION| P=0.297 | |COCH-ARM / FISHERS | P=0.233 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 44/53 (83%) 30/50 (60%) | |POLY-3 RATE (b) | 44/49.96 30/41.31 | |POLY-3 PERCENT (g) | 88.1% 72.6% | |TERMINAL (d) | 22/25 (88%) 10/15 (67%) | |FIRST INCIDENCE | 310 276 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.534 | |POLY 3 | P=0.044N* | |POLY 1.5 | P=0.022N* | |POLY 6 | P=0.078N | |LOGISTIC REGRESSION| P=0.026N* | |COCH-ARM / FISHERS | P=0.008N** | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Lung | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 5/50 (10%) | |POLY-3 RATE (b) | 5/43.26 5/33.26 | |POLY-3 PERCENT (g) | 11.6% 15.0% | |TERMINAL (d) | 1/25 (4%) 2/15 (13%) | |FIRST INCIDENCE | 377 689 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.378 | |POLY 3 | P=0.480 | |POLY 1.5 | P=0.524 | |POLY 6 | P=0.436 | |LOGISTIC REGRESSION| P=0.517 | |COCH-ARM / FISHERS | P=0.592 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 24 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 14/53 (26%) 6/50 (12%) | |POLY-3 RATE (b) | 14/42.58 6/33.73 | |POLY-3 PERCENT (g) | 32.9% 17.8% | |TERMINAL (d) | 11/25 (44%) 3/15 (20%) | |FIRST INCIDENCE | 610 547 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.259N | |POLY 3 | P=0.114N | |POLY 1.5 | P=0.086N | |POLY 6 | P=0.151N | |LOGISTIC REGRESSION| P=0.152N | |COCH-ARM / FISHERS | P=0.054N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Metaplasia Bronchiolar | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 7/50 (14%) | |POLY-3 RATE (b) | 5/41.78 7/33.80 | |POLY-3 PERCENT (g) | 12.0% 20.7% | |TERMINAL (d) | 5/25 (20%) 4/15 (27%) | |FIRST INCIDENCE | 728 (T) 512 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.115 | |POLY 3 | P=0.249 | |POLY 1.5 | P=0.282 | |POLY 6 | P=0.218 | |LOGISTIC REGRESSION| P=0.175 | |COCH-ARM / FISHERS | P=0.339 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 25 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 38/53 (72%) 29/49 (59%) | |POLY-3 RATE (b) | 38/46.17 29/40.93 | |POLY-3 PERCENT (g) | 82.3% 70.9% | |TERMINAL (d) | 24/25 (96%) 10/15 (67%) | |FIRST INCIDENCE | 321 240 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.284 | |POLY 3 | P=0.136N | |POLY 1.5 | P=0.130N | |POLY 6 | P=0.144N | |LOGISTIC REGRESSION| P=0.284N | |COCH-ARM / FISHERS | P=0.131N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/5 (40%) 1/3 (33%) | |POLY-3 RATE (b) | 2/4.62 1/2.95 | |POLY-3 PERCENT (g) | 43.3% 33.9% | |TERMINAL (d) | 1/3 (33%) 1/2 (50%) | |FIRST INCIDENCE | 678 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.662N | |POLY 3 | P=0.720N | |POLY 1.5 | P=0.731N | |POLY 6 | P=0.705N | |LOGISTIC REGRESSION| P=0.689N | |COCH-ARM / FISHERS | P=0.714N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 26 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/5 (40%) 0/3 (0%) | |POLY-3 RATE (b) | 2/4.42 0/2.95 | |POLY-3 PERCENT (g) | 45.2% 0.0% | |TERMINAL (d) | 2/3 (67%) 0/2 (0%) | |FIRST INCIDENCE | 728 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.309N | |POLY 3 | P=0.357N | |POLY 1.5 | P=0.386N | |POLY 6 | P=0.313N | |LOGISTIC REGRESSION| (e) | |COCH-ARM / FISHERS | P=0.357N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Mammary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 3/50 (6%) | |POLY-3 RATE (b) | 1/41.81 3/33.91 | |POLY-3 PERCENT (g) | 2.4% 8.9% | |TERMINAL (d) | 0/25 (0%) 1/15 (7%) | |FIRST INCIDENCE | 720 384 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.185 | |POLY 3 | P=0.253 | |POLY 1.5 | P=0.266 | |POLY 6 | P=0.240 | |LOGISTIC REGRESSION| P=0.278 | |COCH-ARM / FISHERS | P=0.287 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 27 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 33/53 (62%) 19/50 (38%) | |POLY-3 RATE (b) | 33/46.61 19/36.27 | |POLY-3 PERCENT (g) | 70.8% 52.4% | |TERMINAL (d) | 19/25 (76%) 7/15 (47%) | |FIRST INCIDENCE | 289 413 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.350N | |POLY 3 | P=0.060N | |POLY 1.5 | P=0.033N* | |POLY 6 | P=0.099N | |LOGISTIC REGRESSION| P=0.046N* | |COCH-ARM / FISHERS | P=0.012N* | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Mammary Gland | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 2/41.97 1/33.80 | |POLY-3 PERCENT (g) | 4.8% 3.0% | |TERMINAL (d) | 1/25 (4%) 0/15 (0%) | |FIRST INCIDENCE | 678 384 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.605N | |POLY 3 | P=0.604N | |POLY 1.5 | P=0.574N | |POLY 6 | P=0.638N | |LOGISTIC REGRESSION| P=0.487N | |COCH-ARM / FISHERS | P=0.522N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 28 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Nose | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/53 (15%) 7/50 (14%) | |POLY-3 RATE (b) | 8/44.12 7/34.45 | |POLY-3 PERCENT (g) | 18.1% 20.3% | |TERMINAL (d) | 2/25 (8%) 1/15 (7%) | |FIRST INCIDENCE | 321 370 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.437 | |POLY 3 | P=0.535 | |POLY 1.5 | P=0.587 | |POLY 6 | P=0.478 | |LOGISTIC REGRESSION| P=0.571N | |COCH-ARM / FISHERS | P=0.549N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Nose: Respiratory Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 1/42.34 2/33.05 | |POLY-3 PERCENT (g) | 2.4% 6.1% | |TERMINAL (d) | 0/25 (0%) 1/15 (7%) | |FIRST INCIDENCE | 554 701 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.365 | |POLY 3 | P=0.449 | |POLY 1.5 | P=0.462 | |POLY 6 | P=0.437 | |LOGISTIC REGRESSION| P=0.446 | |COCH-ARM / FISHERS | P=0.478 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 29 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Oral Mucosa: Gingival | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/52 (29%) 14/50 (28%) | |POLY-3 RATE (b) | 15/42.71 14/36.02 | |POLY-3 PERCENT (g) | 35.1% 38.9% | |TERMINAL (d) | 9/24 (38%) 5/15 (33%) | |FIRST INCIDENCE | 500 491 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.225 | |POLY 3 | P=0.465 | |POLY 1.5 | P=0.523 | |POLY 6 | P=0.414 | |LOGISTIC REGRESSION| P=0.445 | |COCH-ARM / FISHERS | P=0.550N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Ovary | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 43/53 (81%) 39/47 (83%) | |POLY-3 RATE (b) | 43/50.40 39/43.66 | |POLY-3 PERCENT (g) | 85.3% 89.3% | |TERMINAL (d) | 21/25 (84%) 13/15 (87%) | |FIRST INCIDENCE | 310 276 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.072 | |POLY 3 | P=0.396 | |POLY 1.5 | P=0.422 | |POLY 6 | P=0.395 | |LOGISTIC REGRESSION| P=0.427 | |COCH-ARM / FISHERS | P=0.510 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 30 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/53 (21%) 12/47 (26%) | |POLY-3 RATE (b) | 11/42.65 12/36.25 | |POLY-3 PERCENT (g) | 25.8% 33.1% | |TERMINAL (d) | 8/25 (32%) 4/15 (27%) | |FIRST INCIDENCE | 554 384 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.148 | |POLY 3 | P=0.327 | |POLY 1.5 | P=0.345 | |POLY 6 | P=0.309 | |LOGISTIC REGRESSION| P=0.327 | |COCH-ARM / FISHERS | P=0.371 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Pancreas | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/49 (0%) | |POLY-3 RATE (b) | 2/42.25 0/32.92 | |POLY-3 PERCENT (g) | 4.7% 0.0% | |TERMINAL (d) | 1/25 (4%) 0/15 (0%) | |FIRST INCIDENCE | 588 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.331N | |POLY 3 | P=0.333N | |POLY 1.5 | P=0.303N | |POLY 6 | P=0.372N | |LOGISTIC REGRESSION| P=0.268N | |COCH-ARM / FISHERS | P=0.268N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 31 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 0/49 (0%) | |POLY-3 RATE (b) | 3/42.64 0/32.92 | |POLY-3 PERCENT (g) | 7.0% 0.0% | |TERMINAL (d) | 1/25 (4%) 0/15 (0%) | |FIRST INCIDENCE | 588 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.197N | |POLY 3 | P=0.195N | |POLY 1.5 | P=0.169N | |POLY 6 | P=0.230N | |LOGISTIC REGRESSION| P=0.137N | |COCH-ARM / FISHERS | P=0.136N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Pancreas: Acinus | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/49 (4%) | |POLY-3 RATE (b) | 0/41.78 2/34.20 | |POLY-3 PERCENT (g) | 0.0% 5.9% | |TERMINAL (d) | 0/25 (0%) 0/15 (0%) | |FIRST INCIDENCE | --- 370 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.204 | |POLY 3 | P=0.217 | |POLY 1.5 | P=0.221 | |POLY 6 | P=0.214 | |LOGISTIC REGRESSION| P=0.281 | |COCH-ARM / FISHERS | P=0.228 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 32 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Pituitary Gland | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 20/53 (38%) 13/49 (27%) | |POLY-3 RATE (b) | 20/42.80 13/34.10 | |POLY-3 PERCENT (g) | 46.7% 38.1% | |TERMINAL (d) | 14/25 (56%) 6/15 (40%) | |FIRST INCIDENCE | 651 500 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.550 | |POLY 3 | P=0.305N | |POLY 1.5 | P=0.243N | |POLY 6 | P=0.381N | |LOGISTIC REGRESSION| P=0.435N | |COCH-ARM / FISHERS | P=0.159N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Pituitary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/49 (2%) | |POLY-3 RATE (b) | 2/41.83 1/32.63 | |POLY-3 PERCENT (g) | 4.8% 3.1% | |TERMINAL (d) | 1/25 (4%) 1/15 (7%) | |FIRST INCIDENCE | 715 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.664N | |POLY 3 | P=0.619N | |POLY 1.5 | P=0.587N | |POLY 6 | P=0.654N | |LOGISTIC REGRESSION| P=0.648N | |COCH-ARM / FISHERS | P=0.530N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 33 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Pituitary Gland | | Cytoplasmic Alteration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 2/49 (4%) | |POLY-3 RATE (b) | 1/41.78 2/32.96 | |POLY-3 PERCENT (g) | 2.4% 6.1% | |TERMINAL (d) | 1/25 (4%) 1/15 (7%) | |FIRST INCIDENCE | 728 (T) 638 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.342 | |POLY 3 | P=0.450 | |POLY 1.5 | P=0.461 | |POLY 6 | P=0.440 | |LOGISTIC REGRESSION| P=0.397 | |COCH-ARM / FISHERS | P=0.470 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Pituitary Gland | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 2/49 (4%) | |POLY-3 RATE (b) | 2/42.16 2/32.63 | |POLY-3 PERCENT (g) | 4.7% 6.1% | |TERMINAL (d) | 1/25 (4%) 2/15 (13%) | |FIRST INCIDENCE | 619 728 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.520 | |POLY 3 | P=0.628 | |POLY 1.5 | P=0.645 | |POLY 6 | P=0.611 | |LOGISTIC REGRESSION| P=0.582 | |COCH-ARM / FISHERS | P=0.661 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 34 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 22/53 (42%) 19/49 (39%) | |POLY-3 RATE (b) | 22/43.51 19/37.38 | |POLY-3 PERCENT (g) | 50.6% 50.8% | |TERMINAL (d) | 16/25 (64%) 8/15 (53%) | |FIRST INCIDENCE | 610 384 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.187 | |POLY 3 | P=0.589 | |POLY 1.5 | P=0.563N | |POLY 6 | P=0.562 | |LOGISTIC REGRESSION| P=0.460 | |COCH-ARM / FISHERS | P=0.469N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Skin | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 2/42.17 0/32.95 | |POLY-3 PERCENT (g) | 4.7% 0.0% | |TERMINAL (d) | 0/25 (0%) 0/15 (0%) | |FIRST INCIDENCE | 619 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.338N | |POLY 3 | P=0.333N | |POLY 1.5 | P=0.301N | |POLY 6 | P=0.372N | |LOGISTIC REGRESSION| P=0.278N | |COCH-ARM / FISHERS | P=0.262N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 35 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Skin | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 2/42.17 0/32.95 | |POLY-3 PERCENT (g) | 4.7% 0.0% | |TERMINAL (d) | 0/25 (0%) 0/15 (0%) | |FIRST INCIDENCE | 619 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.338N | |POLY 3 | P=0.333N | |POLY 1.5 | P=0.301N | |POLY 6 | P=0.372N | |LOGISTIC REGRESSION| P=0.278N | |COCH-ARM / FISHERS | P=0.262N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 49/53 (92%) 49/49 (100%) | |POLY-3 RATE (b) | 49/51.40 49/49.00 | |POLY-3 PERCENT (g) | 95.3% 100.0% | |TERMINAL (d) | 25/25 (100%) 15/15 (100%) | |FIRST INCIDENCE | 289 240 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.011 * | |POLY 3 | P=0.164 | |POLY 1.5 | P=0.119 | |POLY 6 | P=0.237 | |LOGISTIC REGRESSION| P=0.053 | |COCH-ARM / FISHERS | P=0.069 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 36 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 52/53 (98%) 48/49 (98%) | |POLY-3 RATE (b) | 52/53.00 48/48.57 | |POLY-3 PERCENT (g) | 98.1% 98.8% | |TERMINAL (d) | 24/25 (96%) 15/15 (100%) | |FIRST INCIDENCE | 289 240 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.041 * | |POLY 3 | P=0.724 | |POLY 1.5 | P=0.756 | |POLY 6 | P=0.661 | |LOGISTIC REGRESSION| P=0.726N | |COCH-ARM / FISHERS | P=0.732N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/53 (13%) 2/49 (4%) | |POLY-3 RATE (b) | 7/44.55 2/33.47 | |POLY-3 PERCENT (g) | 15.7% 6.0% | |TERMINAL (d) | 1/25 (4%) 0/15 (0%) | |FIRST INCIDENCE | 310 625 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.189N | |POLY 3 | P=0.183N | |POLY 1.5 | P=0.147N | |POLY 6 | P=0.231N | |LOGISTIC REGRESSION| P=0.077N | |COCH-ARM / FISHERS | P=0.100N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 37 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Spleen: Red Pulp | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/49 (0%) | |POLY-3 RATE (b) | 2/42.70 0/32.92 | |POLY-3 PERCENT (g) | 4.7% 0.0% | |TERMINAL (d) | 1/25 (4%) 0/15 (0%) | |FIRST INCIDENCE | 310 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.308N | |POLY 3 | P=0.338N | |POLY 1.5 | P=0.307N | |POLY 6 | P=0.376N | |LOGISTIC REGRESSION| P=0.197N | |COCH-ARM / FISHERS | P=0.268N | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 5/50 (10%) | |POLY-3 RATE (b) | 4/42.72 5/35.15 | |POLY-3 PERCENT (g) | 9.4% 14.2% | |TERMINAL (d) | 2/25 (8%) 2/15 (13%) | |FIRST INCIDENCE | 289 370 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.296 | |POLY 3 | P=0.394 | |POLY 1.5 | P=0.419 | |POLY 6 | P=0.368 | |LOGISTIC REGRESSION| P=0.538 | |COCH-ARM / FISHERS | P=0.463 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 38 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Stomach, Glandular | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 3/50 (6%) | |POLY-3 RATE (b) | 2/41.98 3/34.03 | |POLY-3 PERCENT (g) | 4.8% 8.8% | |TERMINAL (d) | 1/25 (4%) 1/15 (7%) | |FIRST INCIDENCE | 675 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.340 | |POLY 3 | P=0.427 | |POLY 1.5 | P=0.447 | |POLY 6 | P=0.405 | |LOGISTIC REGRESSION| P=0.501 | |COCH-ARM / FISHERS | P=0.472 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 43/53 (81%) 44/49 (90%) | |POLY-3 RATE (b) | 43/48.07 44/45.76 | |POLY-3 PERCENT (g) | 89.5% 96.2% | |TERMINAL (d) | 23/25 (92%) 14/15 (93%) | |FIRST INCIDENCE | 377 240 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.009 ** | |POLY 3 | P=0.166 | |POLY 1.5 | P=0.152 | |POLY 6 | P=0.218 | |LOGISTIC REGRESSION| P=0.036 * | |COCH-ARM / FISHERS | P=0.170 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 39 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/53 (28%) 15/48 (31%) | |POLY-3 RATE (b) | 15/43.91 15/35.37 | |POLY-3 PERCENT (g) | 34.2% 42.4% | |TERMINAL (d) | 10/25 (40%) 5/15 (33%) | |FIRST INCIDENCE | 513 384 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.148 | |POLY 3 | P=0.309 | |POLY 1.5 | P=0.367 | |POLY 6 | P=0.260 | |LOGISTIC REGRESSION| P=0.305 | |COCH-ARM / FISHERS | P=0.457 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/53 (13%) 23/48 (48%) | |POLY-3 RATE (b) | 7/42.51 23/41.15 | |POLY-3 PERCENT (g) | 16.5% 55.9% | |TERMINAL (d) | 3/25 (12%) 6/15 (40%) | |FIRST INCIDENCE | 651 276 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** | |POLY 3 | P<0.001 ** | |POLY 1.5 | P<0.001 ** | |POLY 6 | P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 40 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Tooth: Peridontal Tissue | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 33/33 (100%) 24/24 (100%) | |POLY-3 RATE (b) | 33/33.00 24/24.00 | |POLY-3 PERCENT (g) | 100.0% 100.0% | |TERMINAL (d) | 19/19 (100%) 9/9 (100%) | |FIRST INCIDENCE | 289 276 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) | |POLY 3 | (e) | |POLY 1.5 | (e) | |POLY 6 | (e) | |LOGISTIC REGRESSION| (e) | |COCH-ARM / FISHERS | (e) | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Urinary Bladder | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 2/41.83 2/33.62 | |POLY-3 PERCENT (g) | 4.8% 6.0% | |TERMINAL (d) | 1/25 (4%) 1/15 (7%) | |FIRST INCIDENCE | 715 500 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.537 | |POLY 3 | P=0.638 | |POLY 1.5 | P=0.652 | |POLY 6 | P=0.623 | |LOGISTIC REGRESSION| P=0.632 | |COCH-ARM / FISHERS | P=0.669 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 41 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Urinary Bladder: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 3/50 (6%) | |POLY-3 RATE (b) | 0/41.78 3/33.67 | |POLY-3 PERCENT (g) | 0.0% 8.9% | |TERMINAL (d) | 0/25 (0%) 1/15 (7%) | |FIRST INCIDENCE | --- 500 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.065 | |POLY 3 | P=0.096 | |POLY 1.5 | P=0.101 | |POLY 6 | P=0.091 | |LOGISTIC REGRESSION| P=0.098 | |COCH-ARM / FISHERS | P=0.111 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Uterus | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 3/49 (6%) | |POLY-3 RATE (b) | 3/42.38 3/33.17 | |POLY-3 PERCENT (g) | 7.1% 9.1% | |TERMINAL (d) | 2/25 (8%) 0/15 (0%) | |FIRST INCIDENCE | 536 491 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.478 | |POLY 3 | P=0.569 | |POLY 1.5 | P=0.592 | |POLY 6 | P=0.548 | |LOGISTIC REGRESSION| P=0.600 | |COCH-ARM / FISHERS | P=0.623 | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 42 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Uterus | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 7/49 (14%) | |POLY-3 RATE (b) | 0/41.78 7/34.56 | |POLY-3 PERCENT (g) | 0.0% 20.3% | |TERMINAL (d) | 0/25 (0%) 2/15 (13%) | |FIRST INCIDENCE | --- 276 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** | |POLY 3 | P=0.003 ** | |POLY 1.5 | P=0.004 ** | |POLY 6 | P=0.003 ** | |LOGISTIC REGRESSION| P=0.008 ** | |COCH-ARM / FISHERS | P=0.005 ** | |ORDER RESTRICTED | (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Uterus | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 17/53 (32%) 28/49 (57%) | |POLY-3 RATE (b) | 17/45.44 28/39.23 | |POLY-3 PERCENT (g) | 37.4% 71.4% | |TERMINAL (d) | 8/25 (32%) 12/15 (80%) | |FIRST INCIDENCE | 321 451 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** | |POLY 3 | P<0.001 ** | |POLY 1.5 | P=0.002 ** | |POLY 6 | P<0.001 ** | |LOGISTIC REGRESSION| P=0.003 ** | |COCH-ARM / FISHERS | P=0.009 ** | |ORDER RESTRICTED | (e) | |=================================================================================================================================| Date: 09/30/03 EXPERIMENT: 96007 TEST: 05 Page 43 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 200 NG/ | | | KG STOP | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 31/53 (58%) 35/49 (71%) | |POLY-3 RATE (b) | 31/47.62 35/43.22 | |POLY-3 PERCENT (g) | 65.1% 81.0% | |TERMINAL (d) | 16/25 (64%) 12/15 (80%) | |FIRST INCIDENCE | 310 215 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.011 * | |POLY 3 | P=0.062 | |POLY 1.5 | P=0.080 | |POLY 6 | P=0.049 * | |LOGISTIC REGRESSION| P=0.084 | |COCH-ARM / FISHERS | P=0.123 | |ORDER RESTRICTED | (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).