TDMS Study 93029-03 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: NCTR LEUKOMALACHITE GREEN DATE: 05/05/03 EXPERIMENT: 93029 TEST: 03 TIME: 14:28:19 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: 224-93-00001 ROUTE: DOSED FEED NTP C#: C93029 PATHOLOGIST: MISSING CAS: 129-73-7 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF LEUKOMALACHITE GREEN =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Adrenal Gland: Cortex Hyperplasia Focal Brain: Brain Stem, Hypothalamus Compression Eye Hemorrhage Eye: Bilateral, Retina Degeneration Eye: Retina Degeneration Intestine Large: Cecum, Lymphoid Tissue Hyperplasia Kidney Nephropathy Pigmentation Liver Degeneration Cystic Eosinophilic Focus Vacuolization Cytoplasmic Liver: Bile Duct Hyperplasia Liver: Centrilobular Necrosis Lung: Alveolar Epithelium Hyperplasia Mammary Gland Galactocele Mammary Gland: Duct Dilatation Pancreas: Acinus Atrophy Pancreas: Artery Inflammation Chronic Pituitary Gland: Pars Distalis Hyperplasia Preputial Gland Atrophy Inflammation Prostate Inflammation Prostate: Ventral Hyperplasia Seminal Vesicle Decreased Secretory Fluid Skin: Epithelium Hyperplasia Spleen Fibrosis Hematopoietic Cell Proliferation Hyperplasia Lymphoid Testes: Interstitial Cell Hyperplasia Testes: Seminiferous Tubule Atrophy Thyroid Gland: C-Cell Hyperplasia Thyroid Gland: Follicle Cyst =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Gland: Cortex Angiectasis Bone: Femur Fibrous Osteodystrophy Clitoral Gland: Duct Dilatation Eye Cataract Eye: Retina Degeneration Liver Basophilic Focus Eosinophilic Focus Inflammation Granulomatous Focal Vacuolization Cytoplasmic NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: NCTR LEUKOMALACHITE GREEN DATE: 05/05/03 EXPERIMENT: 93029 TEST: 03 TIME: 14:28:19 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: 224-93-00001 ROUTE: DOSED FEED NTP C#: C93029 PATHOLOGIST: MISSING CAS: 129-73-7 Lymph Node: Mandibular Infiltration Cellular Plasma Cell Mammary Gland Galactocele Mammary Gland: Duct Dilatation Mesentery: Fat Necrosis Pituitary Gland: Pars Distalis Cyst Thyroid Gland: C-Cell Hyperplasia Thyroid Gland: Follicular Cell Hyperplasia =============================================================== Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Adrenal Gland: Cortex | | Accessory Adrenal Cortical Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 0/46 (0%) 2/47 (4%) 1/47 (2%) |0/47 (0%) 0/48 (0%) 3/46 (7%) 0/48 (0%) | |POLY-3 RATE (b) | 0/40.39 0/41.07 2/42.02 1/42.42 |0/42.64 0/44.68 3/41.67 0/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.8% 2.4% |0.0% 0.0% 7.2% 0.0% | |TERMINAL (d) | 0/23 (0%) 0/29 (0%) 2/33 (6%) 1/30 (3%) |0/32 (0%) 0/36 (0%) 3/33 (9%) 0/34 (0%) | |FIRST INCIDENCE | --- --- 733 (T) 733 (T) |--- --- 734 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.261 (e) P=0.321 P=0.553 |P=0.502 (e) P=0.126 (e) | |POLY 3 | P=0.237 (e) P=0.246 P=0.510 |P=0.480 (e) P=0.114 (e) | |POLY 1.5 | P=0.232 (e) P=0.241 P=0.505 |P=0.490 (e) P=0.112 (e) | |POLY 6 | P=0.246 (e) P=0.257 P=0.517 |P=0.471 (e) P=0.118 (e) | |LOGISTIC REGRESSION| (e) (e) P=0.321 P=0.553 |(e) (e) P=0.126 (e) | |COCH-ARM / FISHERS | P=0.225 (e) P=0.247 P=0.500 |P=0.501 (e) P=0.117 (e) | |ORDER RESTRICTED | P=0.174 (e) (e) (e) |P=0.158 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Adrenal Gland: Cortex | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 0/46 (0%) 0/47 (0%) 0/47 (0%) |8/47 (17%) 10/48 (21%) 2/46 (4%) 3/48 (6%) | |POLY-3 RATE (b) | 0/40.39 0/41.07 0/42.02 0/42.42 |8/42.64 10/44.69 2/41.73 3/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |18.8% 22.4% 4.8% 7.0% | |TERMINAL (d) | 0/23 (0%) 0/29 (0%) 0/33 (0%) 0/30 (0%) |8/32 (25%) 9/36 (25%) 1/33 (3%) 3/34 (9%) | |FIRST INCIDENCE | --- --- --- --- |734 (T) 732 719 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.014N* P=0.506 P=0.041N* P=0.078N | |POLY 3 | (e) (e) (e) (e) |P=0.016N* P=0.439 P=0.047N* P=0.096N | |POLY 1.5 | (e) (e) (e) (e) |P=0.016N* P=0.421 P=0.050N P=0.096N | |POLY 6 | (e) (e) (e) (e) |P=0.016N* P=0.468 P=0.043N* P=0.095N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.014N* (e) P=0.039N* P=0.078N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.016N* P=0.416 P=0.049N* P=0.093N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.030N* (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Adrenal Gland: Cortex | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 5/46 (11%) 3/47 (6%) 5/47 (11%) |4/47 (9%) 2/48 (4%) 4/46 (9%) 5/48 (10%) | |POLY-3 RATE (b) | 0/40.39 5/41.07 3/42.02 5/42.45 |4/42.64 2/44.68 4/41.67 5/42.63 | |POLY-3 PERCENT (g) | 0.0% 12.2% 7.1% 11.8% |9.4% 4.5% 9.6% 11.7% | |TERMINAL (d) | 0/23 (0%) 5/29 (17%) 3/33 (9%) 4/30 (13%) |4/32 (13%) 2/36 (6%) 4/33 (12%) 5/34 (15%) | |FIRST INCIDENCE | --- 733 (T) 733 (T) 724 |734 (T) 734 (T) 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.156 P=0.054 P=0.191 P=0.058 |P=0.282 P=0.283N P=0.629N P=0.539 | |POLY 3 | P=0.121 P=0.031 * P=0.125 P=0.034 * |P=0.265 P=0.316N P=0.631 P=0.500 | |POLY 1.5 | P=0.113 P=0.030 * P=0.121 P=0.032 * |P=0.274 P=0.325N P=0.625 P=0.503 | |POLY 6 | P=0.134 P=0.034 * P=0.134 P=0.037 * |P=0.257 P=0.302N P=0.644 P=0.501 | |LOGISTIC REGRESSION| P=0.129 P=0.054 P=0.191 P=0.047 * |P=0.282 P=0.283N P=0.629N P=0.539 | |COCH-ARM / FISHERS | P=0.107 P=0.026 * P=0.121 P=0.028 * |P=0.284 P=0.329N P=0.631 P=0.514 | |ORDER RESTRICTED | P=0.031 * (e) (e) (e) |P=0.341 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Adrenal Gland: Cortex | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 1/46 (2%) 0/47 (0%) 1/47 (2%) |2/47 (4%) 0/48 (0%) 2/46 (4%) 0/48 (0%) | |POLY-3 RATE (b) | 0/40.39 1/41.07 0/42.02 1/42.42 |2/42.64 0/44.68 2/42.05 0/42.63 | |POLY-3 PERCENT (g) | 0.0% 2.4% 0.0% 2.4% |4.7% 0.0% 4.8% 0.0% | |TERMINAL (d) | 0/23 (0%) 1/29 (3%) 0/33 (0%) 1/30 (3%) |2/32 (6%) 0/36 (0%) 1/33 (3%) 0/34 (0%) | |FIRST INCIDENCE | --- 733 (T) --- 733 (T) |734 (T) --- 626 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.482 P=0.546 (e) P=0.553 |P=0.290N P=0.213N P=0.685N P=0.225N | |POLY 3 | P=0.454 P=0.503 (e) P=0.510 |P=0.301N P=0.227N P=0.689 P=0.237N | |POLY 1.5 | P=0.447 P=0.500 (e) P=0.505 |P=0.295N P=0.231N P=0.684 P=0.236N | |POLY 6 | P=0.465 P=0.510 (e) P=0.517 |P=0.308N P=0.220N P=0.689N P=0.236N | |LOGISTIC REGRESSION| (e) P=0.546 (e) P=0.553 |P=0.290N (e) P=0.686 (e) | |COCH-ARM / FISHERS | P=0.440 P=0.495 (e) P=0.500 |P=0.289N P=0.242N P=0.683 P=0.242N | |ORDER RESTRICTED | P=0.261 (e) (e) (e) |P=0.115N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Adrenal Gland: Cortex | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/47 (2%) 2/46 (4%) 4/47 (9%) 2/47 (4%) |2/47 (4%) 0/48 (0%) 0/46 (0%) 1/48 (2%) | |POLY-3 RATE (b) | 1/40.75 2/41.87 4/42.66 2/42.59 |2/42.94 0/44.68 0/41.67 1/42.64 | |POLY-3 PERCENT (g) | 2.5% 4.8% 9.4% 4.7% |4.7% 0.0% 0.0% 2.4% | |TERMINAL (d) | 0/23 (0%) 0/29 (0%) 2/33 (6%) 1/30 (3%) |1/32 (3%) 0/36 (0%) 0/33 (0%) 0/34 (0%) | |FIRST INCIDENCE | 632 615 543 687 |653 --- --- 733 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.432 P=0.500 P=0.249 P=0.551 |P=0.503N P=0.222N P=0.234N P=0.495N | |POLY 3 | P=0.406 P=0.509 P=0.192 P=0.515 |P=0.502N P=0.228N P=0.244N P=0.502N | |POLY 1.5 | P=0.397 P=0.501 P=0.184 P=0.508 |P=0.499N P=0.232N P=0.245N P=0.499N | |POLY 6 | P=0.420 P=0.524 P=0.208 P=0.528 |P=0.506N P=0.223N P=0.240N P=0.504N | |LOGISTIC REGRESSION| P=0.367 P=0.480 P=0.178 P=0.485 |P=0.498N P=0.229N P=0.237N P=0.495N | |COCH-ARM / FISHERS | P=0.386 P=0.492 P=0.181 P=0.500 |P=0.496N P=0.242N P=0.253N P=0.492N | |ORDER RESTRICTED | P=0.283 (e) (e) (e) |P=0.132N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Adrenal Gland: Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/47 (2%) 0/46 (0%) 3/47 (6%) 2/47 (4%) |1/47 (2%) 0/48 (0%) 0/46 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 1/40.39 0/41.07 3/42.02 2/42.42 |1/43.00 0/44.68 0/41.67 0/42.63 | |POLY-3 PERCENT (g) | 2.5% 0.0% 7.1% 4.7% |2.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/23 (4%) 0/29 (0%) 3/33 (9%) 2/30 (7%) |0/32 (0%) 0/36 (0%) 0/33 (0%) 0/34 (0%) | |FIRST INCIDENCE | 733 (T) --- 733 (T) 733 (T) |635 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.262 P=0.454N P=0.441 P=0.593 |P=0.337N P=0.495N P=0.500N P=0.510N | |POLY 3 | P=0.222 P=0.497N P=0.319 P=0.517 |P=0.330N P=0.492N P=0.506N P=0.502N | |POLY 1.5 | P=0.216 P=0.500N P=0.311 P=0.509 |P=0.329N P=0.496N P=0.508N P=0.500N | |POLY 6 | P=0.229 P=0.490N P=0.337 P=0.530 |P=0.332N P=0.488N P=0.503N P=0.503N | |LOGISTIC REGRESSION| P=0.262 (e) P=0.441 P=0.593 |P=0.324N P=0.466N P=0.467N P=0.435N | |COCH-ARM / FISHERS | P=0.210 P=0.505N P=0.308 P=0.500 |P=0.329N P=0.495N P=0.505N P=0.495N | |ORDER RESTRICTED | P=0.198 (e) (e) (e) |P=0.122N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Bone Marrow | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 1/47 (2%) 0/48 (0%) 1/47 (2%) |4/48 (8%) 2/48 (4%) 4/48 (8%) 3/48 (6%) | |POLY-3 RATE (b) | 1/41.66 1/42.07 0/43.02 1/42.68 |4/44.60 2/44.68 4/44.06 3/43.16 | |POLY-3 PERCENT (g) | 2.4% 2.4% 0.0% 2.3% |9.0% 4.5% 9.1% 7.0% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |2/33 (6%) 2/36 (6%) 2/35 (6%) 2/34 (6%) | |FIRST INCIDENCE | 659 732 --- 661 |552 734 (T) 657 570 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.571N P=0.734N P=0.480N P=0.737N |P=0.561N P=0.315N P=0.621N P=0.501N | |POLY 3 | P=0.599N P=0.759N P=0.494N P=0.755N |P=0.569N P=0.336N P=0.637 P=0.518N | |POLY 1.5 | P=0.601N P=0.759 P=0.498N P=0.760N |P=0.560N P=0.341N P=0.633 P=0.512N | |POLY 6 | P=0.595N P=0.753N P=0.485N P=0.748N |P=0.569 P=0.328N P=0.641N P=0.521N | |LOGISTIC REGRESSION| P=0.610N P=0.757 P=0.493N P=0.745 |P=0.543N P=0.324N P=0.626N P=0.435N | |COCH-ARM / FISHERS | P=0.603N P=0.747 P=0.500N P=0.747 |P=0.550N P=0.339N P=0.643N P=0.500N | |ORDER RESTRICTED | P=0.527N (e) (e) (e) |P=0.551N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 0/47 (0%) 0/48 (0%) 2/47 (4%) |0/48 (0%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 2/41.39 0/42.07 0/43.02 2/42.42 |0/43.64 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 4.8% 0.0% 0.0% 4.7% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/24 (8%) 0/30 (0%) 0/34 (0%) 2/30 (7%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 733 (T) --- --- 733 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.508 P=0.190N P=0.165N P=0.613N |(e) (e) (e) (e) | |POLY 3 | P=0.454 P=0.233N P=0.228N P=0.685N |(e) (e) (e) (e) | |POLY 1.5 | P=0.453 P=0.238N P=0.234N P=0.693N |(e) (e) (e) (e) | |POLY 6 | P=0.454 P=0.226N P=0.218N P=0.673N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.508 (e) (e) P=0.613N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.453 P=0.253N P=0.247N P=0.684 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.259N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Bone Marrow: Myeloid Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 1/47 (2%) 2/48 (4%) 1/47 (2%) |0/48 (0%) 1/48 (2%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 0/41.39 1/42.07 2/43.91 1/43.09 |0/43.64 1/45.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 0.0% 2.4% 4.6% 2.3% |0.0% 2.2% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 1/30 (3%) 0/34 (0%) 0/30 (0%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 733 (T) 543 505 |--- 60 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.385 P=0.545 P=0.246 P=0.492 |P=0.500N P=0.500 (e) (e) | |POLY 3 | P=0.393 P=0.503 P=0.250 P=0.508 |P=0.494N P=0.509 (e) (e) | |POLY 1.5 | P=0.381 P=0.500 P=0.243 P=0.502 |P=0.498N P=0.505 (e) (e) | |POLY 6 | P=0.409 P=0.510 P=0.264 P=0.516 |P=0.488N P=0.515 (e) (e) | |LOGISTIC REGRESSION| P=0.366 P=0.545 P=0.290 P=0.866 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.366 P=0.495 P=0.247 P=0.495 |P=0.500N P=0.500 (e) (e) | |ORDER RESTRICTED | P=0.237 (e) (e) (e) |P=0.393N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Bone: Femur | | Fibrous Osteodystrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/47 (0%) 0/48 (0%) 2/47 (4%) |2/48 (4%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 1/41.39 0/42.07 0/43.02 2/42.59 |2/44.22 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 4.7% |4.5% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/24 (4%) 0/30 (0%) 0/34 (0%) 1/30 (3%) |1/33 (3%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 733 (T) --- --- 687 |552 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.248 P=0.455N P=0.431N P=0.562 |P=0.142N P=0.232N P=0.240N P=0.244N | |POLY 3 | P=0.223 P=0.497N P=0.492N P=0.510 |P=0.138N P=0.235N P=0.240N P=0.245N | |POLY 1.5 | P=0.222 P=0.500N P=0.497N P=0.502 |P=0.137N P=0.238N P=0.241N P=0.243N | |POLY 6 | P=0.225 P=0.490N P=0.483N P=0.524 |P=0.139N P=0.230N P=0.236N P=0.247N | |LOGISTIC REGRESSION| P=0.231 (e) (e) P=0.522 |P=0.132N P=0.202N P=0.195N P=0.173N | |COCH-ARM / FISHERS | P=0.221 P=0.505N P=0.500N P=0.492 |P=0.138N P=0.247N P=0.247N P=0.247N | |ORDER RESTRICTED | P=0.136 (e) (e) (e) |P=0.032N* (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Bone: Femur | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 0/48 (0%) 0/47 (0%) |1/48 (2%) 4/48 (8%) 3/48 (6%) 1/48 (2%) | |POLY-3 RATE (b) | 0/41.39 0/42.07 0/43.02 0/42.42 |1/43.64 4/44.76 3/43.67 1/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.3% 8.9% 6.9% 2.4% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |1/33 (3%) 3/36 (8%) 3/35 (9%) 1/34 (3%) | |FIRST INCIDENCE | --- --- --- --- |734 (T) 714 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.386N P=0.208 P=0.326 P=0.755N | |POLY 3 | (e) (e) (e) (e) |P=0.397N P=0.186 P=0.305 P=0.755 | |POLY 1.5 | (e) (e) (e) (e) |P=0.393N P=0.180 P=0.302 P=0.757 | |POLY 6 | (e) (e) (e) (e) |P=0.398N P=0.196 P=0.313 P=0.756 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.396N P=0.205 P=0.326 P=0.755N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.383N P=0.181 P=0.308 P=0.753N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.339 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Bone: Sternum | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 0/48 (0%) 0/47 (0%) |1/48 (2%) 4/48 (8%) 4/48 (8%) 1/48 (2%) | |POLY-3 RATE (b) | 0/41.39 0/42.07 0/43.02 0/42.42 |1/43.64 4/44.76 4/43.67 1/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.3% 8.9% 9.2% 2.4% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |1/33 (3%) 3/36 (8%) 4/35 (11%) 1/34 (3%) | |FIRST INCIDENCE | --- --- --- --- |734 (T) 714 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.419N P=0.208 P=0.196 P=0.755N | |POLY 3 | (e) (e) (e) (e) |P=0.434N P=0.186 P=0.178 P=0.755 | |POLY 1.5 | (e) (e) (e) (e) |P=0.428N P=0.180 P=0.175 P=0.757 | |POLY 6 | (e) (e) (e) (e) |P=0.436N P=0.196 P=0.185 P=0.756 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.430N P=0.205 P=0.196 P=0.755N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.417N P=0.181 P=0.181 P=0.753N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.288 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Bone: Turbinate | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 0/48 (0%) 0/47 (0%) |1/48 (2%) 3/48 (6%) 4/48 (8%) 1/48 (2%) | |POLY-3 RATE (b) | 0/41.39 0/42.07 0/43.02 0/42.42 |1/43.64 3/44.76 4/43.67 1/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.3% 6.7% 9.2% 2.4% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |1/33 (3%) 2/36 (6%) 4/35 (11%) 1/34 (3%) | |FIRST INCIDENCE | --- --- --- --- |734 (T) 714 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.504N P=0.337 P=0.196 P=0.755N | |POLY 3 | (e) (e) (e) (e) |P=0.519N P=0.314 P=0.178 P=0.755 | |POLY 1.5 | (e) (e) (e) (e) |P=0.512N P=0.307 P=0.175 P=0.757 | |POLY 6 | (e) (e) (e) (e) |P=0.522N P=0.325 P=0.185 P=0.756 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.516N P=0.333 P=0.196 P=0.755N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.501N P=0.308 P=0.181 P=0.753N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.338 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Brain: Brain Stem | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 2/47 (4%) 0/48 (0%) 0/47 (0%) |1/48 (2%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 1/41.68 2/43.28 0/43.02 0/42.42 |1/43.87 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 2.4% 4.6% 0.0% 0.0% |2.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 653 487 --- --- |673 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.153N P=0.500 P=0.485N P=0.480N |P=0.335N P=0.475N P=0.480N P=0.505N | |POLY 3 | P=0.150N P=0.513 P=0.494N P=0.497N |P=0.330N P=0.496N P=0.501N P=0.506N | |POLY 1.5 | P=0.153N P=0.504 P=0.498N P=0.500N |P=0.330N P=0.500N P=0.503N P=0.504N | |POLY 6 | P=0.145N P=0.527 P=0.485N P=0.491N |P=0.331N P=0.492N P=0.497N P=0.507N | |LOGISTIC REGRESSION| P=0.107N P=0.516 P=0.490N P=0.516N |P=0.326N P=0.489N P=0.486N P=0.478N | |COCH-ARM / FISHERS | P=0.156N P=0.492 P=0.500N P=0.505N |P=0.330N P=0.500N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.171N (e) (e) (e) |P=0.126N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Brain: Brain Stem, Hypothalamus | | Compression | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/48 (19%) 4/47 (9%) 6/48 (13%) 1/47 (2%) |11/48 (23%) 6/48 (13%) 5/48 (10%) 5/48 (10%) | |POLY-3 RATE (b) | 9/43.29 4/43.34 6/43.28 1/42.62 |11/44.55 6/45.20 5/43.77 5/42.99 | |POLY-3 PERCENT (g) | 20.8% 9.2% 13.9% 2.4% |24.7% 13.3% 11.4% 11.6% | |TERMINAL (d) | 2/24 (8%) 0/30 (0%) 5/34 (15%) 0/30 (0%) |6/33 (18%) 4/36 (11%) 4/35 (11%) 4/34 (12%) | |FIRST INCIDENCE | 541 567 662 679 |662 605 709 632 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.014N* P=0.100N P=0.164N P=0.009N** |P=0.097N P=0.118N P=0.078N P=0.093N | |POLY 3 | P=0.017N* P=0.113N P=0.285N P=0.008N** |P=0.098N P=0.132N P=0.088N P=0.094N | |POLY 1.5 | P=0.017N* P=0.118N P=0.291N P=0.008N** |P=0.093N P=0.141N P=0.090N P=0.091N | |POLY 6 | P=0.017N* P=0.103N P=0.268N P=0.007N** |P=0.104N P=0.122N P=0.084N P=0.097N | |LOGISTIC REGRESSION| P=0.020N* P=0.145N P=0.291N P=0.013N* |P=0.093N P=0.142N P=0.085N P=0.091N | |COCH-ARM / FISHERS | P=0.018N* P=0.124N P=0.288N P=0.008N** |P=0.087N P=0.142N P=0.085N P=0.085N | |ORDER RESTRICTED | P=0.004N** (e) (e) (e) |P=0.064N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Clitoral Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |4/47 (9%) 4/47 (9%) 5/46 (11%) 3/47 (6%) | |POLY-3 RATE (b) | |4/43.22 4/43.85 5/41.83 3/42.13 | |POLY-3 PERCENT (g) | |9.3% 9.1% 12.0% 7.1% | |TERMINAL (d) | |3/33 (9%) 4/36 (11%) 5/35 (14%) 3/34 (9%) | |FIRST INCIDENCE | |718 734 (T) 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.432N P=0.597N P=0.535 P=0.486N | |POLY 3 | |P=0.457N P=0.635N P=0.480 P=0.514N | |POLY 1.5 | |P=0.448N P=0.643 P=0.476 P=0.510N | |POLY 6 | |P=0.463N P=0.622N P=0.490 P=0.515N | |LOGISTIC REGRESSION| |P=0.446N P=0.592N P=0.523 P=0.500N | |COCH-ARM / FISHERS | |P=0.434N P=0.643N P=0.486 P=0.500N | |ORDER RESTRICTED | |P=0.504N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |23/47 (49%) 31/47 (66%) 22/46 (48%) 28/47 (60%) | |POLY-3 RATE (b) | |23/45.16 31/46.44 22/43.69 28/44.84 | |POLY-3 PERCENT (g) | |50.9% 66.8% 50.4% 62.5% | |TERMINAL (d) | |16/33 (49%) 23/36 (64%) 17/35 (49%) 21/34 (62%) | |FIRST INCIDENCE | |552 60 470 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.400 P=0.192 P=0.420N P=0.253 | |POLY 3 | |P=0.357 P=0.089 P=0.563N P=0.184 | |POLY 1.5 | |P=0.366 P=0.080 P=0.569N P=0.187 | |POLY 6 | |P=0.360 P=0.105 P=0.552N P=0.192 | |LOGISTIC REGRESSION| |P=0.405 P=0.071 P=0.549N P=0.198 | |COCH-ARM / FISHERS | |P=0.404 P=0.072 P=0.540N P=0.204 | |ORDER RESTRICTED | |P=0.206 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Clitoral Gland: Duct | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |25/47 (53%) 24/47 (51%) 18/46 (39%) 15/47 (32%) | |POLY-3 RATE (b) | |25/44.40 24/44.59 18/42.15 15/43.56 | |POLY-3 PERCENT (g) | |56.3% 53.8% 42.7% 34.4% | |TERMINAL (d) | |21/33 (64%) 20/36 (56%) 16/35 (46%) 12/34 (35%) | |FIRST INCIDENCE | |552 561 676 405 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.013N* P=0.343N P=0.068N P=0.028N* | |POLY 3 | |P=0.012N* P=0.491N P=0.143N P=0.029N* | |POLY 1.5 | |P=0.012N* P=0.514N P=0.146N P=0.029N* | |POLY 6 | |P=0.012N* P=0.454N P=0.131N P=0.027N* | |LOGISTIC REGRESSION| |P=0.015N* P=0.464N P=0.117N P=0.034N* | |COCH-ARM / FISHERS | |P=0.012N* P=0.500N P=0.125N P=0.030N* | |ORDER RESTRICTED | |P=0.024N* (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Coagulating Gland | | Decreased Secretory Fluid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/46 (4%) 0/45 (0%) 0/47 (0%) 3/46 (7%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 RATE (b) | 2/39.73 0/40.54 0/42.02 3/42.06 |0/0.00 0/0.00 0/0.00 0/0.00 | |POLY-3 PERCENT (g) | 5.0% 0.0% 0.0% 7.1% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/22 (5%) 0/30 (0%) 0/33 (0%) 0/30 (0%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 639 --- --- 661 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.248 P=0.209N P=0.188N P=0.568 |(e) (e) (e) (e) | |POLY 3 | P=0.218 P=0.232N P=0.224N P=0.526 |(e) (e) (e) (e) | |POLY 1.5 | P=0.217 P=0.237N P=0.229N P=0.513 |(e) (e) (e) (e) | |POLY 6 | P=0.219 P=0.224N P=0.215N P=0.547 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.213 P=0.249N P=0.234N P=0.488 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.218 P=0.253N P=0.242N P=0.500 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.111 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Eye | | Cataract | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/48 (10%) 3/47 (6%) 3/48 (6%) 4/47 (9%) |3/48 (6%) 1/48 (2%) 0/48 (0%) 7/48 (15%) | |POLY-3 RATE (b) | 5/42.13 3/43.04 3/43.84 4/42.67 |3/44.00 1/45.12 0/43.67 7/43.24 | |POLY-3 PERCENT (g) | 11.9% 7.0% 6.8% 9.4% |6.8% 2.2% 0.0% 16.2% | |TERMINAL (d) | 3/24 (13%) 1/30 (3%) 1/34 (3%) 2/30 (7%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 6/34 (18%) | |FIRST INCIDENCE | 623 567 439 676 |673 605 --- 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.435N P=0.302N P=0.251N P=0.395N |P=0.029 * P=0.282N P=0.113N P=0.171 | |POLY 3 | P=0.499N P=0.344N P=0.334N P=0.492N |P=0.024 * P=0.296N P=0.120N P=0.149 | |POLY 1.5 | P=0.503N P=0.356N P=0.346N P=0.502N |P=0.025 * P=0.303N P=0.121N P=0.152 | |POLY 6 | P=0.493N P=0.325N P=0.312N P=0.475N |P=0.023 * P=0.286N P=0.117N P=0.148 | |LOGISTIC REGRESSION| P=0.528N P=0.395N P=0.352N P=0.505N |P=0.030 * P=0.288N P=0.120N P=0.156 | |COCH-ARM / FISHERS | P=0.507N P=0.369N P=0.357N P=0.514N |P=0.029 * P=0.308N P=0.121N P=0.158 | |ORDER RESTRICTED | P=0.399N (e) (e) (e) |P=0.006 ** (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Eye | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 0/47 (0%) 0/48 (0%) 0/47 (0%) |0/48 (0%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 2/41.93 0/42.07 0/43.02 0/42.42 |0/43.64 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 4.8% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/24 (4%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 564 --- --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.130N P=0.218N P=0.208N P=0.220N |(e) (e) (e) (e) | |POLY 3 | P=0.140N P=0.236N P=0.231N P=0.234N |(e) (e) (e) (e) | |POLY 1.5 | P=0.139N P=0.239N P=0.235N P=0.238N |(e) (e) (e) (e) | |POLY 6 | P=0.142N P=0.230N P=0.222N P=0.228N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.136N P=0.251N P=0.219N P=0.253N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.139N P=0.253N P=0.247N P=0.253N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.028N* (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Eye | | Phthisis Bulbi | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 0/48 (0%) 0/47 (0%) |0/48 (0%) 1/48 (2%) 1/48 (2%) 2/48 (4%) | |POLY-3 RATE (b) | 0/41.39 0/42.07 0/43.02 0/42.42 |0/43.64 1/44.68 1/43.67 2/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 2.2% 2.3% 4.7% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |0/33 (0%) 1/36 (3%) 1/35 (3%) 2/34 (6%) | |FIRST INCIDENCE | --- --- --- --- |--- 734 (T) 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.158 P=0.517 P=0.512 P=0.245 | |POLY 3 | (e) (e) (e) (e) |P=0.154 P=0.505 P=0.500 P=0.232 | |POLY 1.5 | (e) (e) (e) (e) |P=0.157 P=0.501 P=0.498 P=0.233 | |POLY 6 | (e) (e) (e) (e) |P=0.153 P=0.510 P=0.505 P=0.232 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) P=0.517 P=0.512 P=0.245 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.160 P=0.500 P=0.500 P=0.247 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.114 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Eye: Bilateral | | Cataract | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 0/47 (0%) 1/48 (2%) 3/47 (6%) |1/48 (2%) 1/48 (2%) 0/48 (0%) 2/48 (4%) | |POLY-3 RATE (b) | 2/41.75 0/42.07 1/43.06 3/42.67 |1/43.71 1/45.12 0/43.67 2/42.63 | |POLY-3 PERCENT (g) | 4.8% 0.0% 2.3% 7.0% |2.3% 2.2% 0.0% 4.7% | |TERMINAL (d) | 1/24 (4%) 0/30 (0%) 0/34 (0%) 1/30 (3%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 2/34 (6%) | |FIRST INCIDENCE | 632 --- 724 676 |718 605 --- 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.241 P=0.218N P=0.425N P=0.573 |P=0.366 P=0.749N P=0.495N P=0.507 | |POLY 3 | P=0.209 P=0.235N P=0.489N P=0.510 |P=0.362 P=0.753N P=0.500N P=0.491 | |POLY 1.5 | P=0.207 P=0.239N P=0.496N P=0.500 |P=0.366 P=0.758N P=0.502N P=0.494 | |POLY 6 | P=0.212 P=0.229N P=0.474N P=0.525 |P=0.359 P=0.746N P=0.496N P=0.491 | |LOGISTIC REGRESSION| P=0.206 P=0.249N P=0.500N P=0.492 |P=0.372 P=0.750N P=0.500N P=0.496 | |COCH-ARM / FISHERS | P=0.204 P=0.253N P=0.500N P=0.490 |P=0.371 P=0.753N P=0.500N P=0.500 | |ORDER RESTRICTED | P=0.192 (e) (e) (e) |P=0.260 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Eye: Bilateral, Retina | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/44 (2%) 0/42 (0%) 0/45 (0%) 5/44 (11%) |4/43 (9%) 4/47 (9%) 5/47 (11%) 7/45 (16%) | |POLY-3 RATE (b) | 1/37.79 0/39.05 0/40.96 5/39.87 |4/39.95 4/44.12 5/42.91 7/41.16 | |POLY-3 PERCENT (g) | 2.7% 0.0% 0.0% 12.5% |10.0% 9.1% 11.7% 17.0% | |TERMINAL (d) | 1/22 (5%) 0/30 (0%) 0/34 (0%) 5/30 (17%) |3/32 (9%) 4/36 (11%) 4/35 (11%) 7/34 (21%) | |FIRST INCIDENCE | 733 (T) --- --- 733 (T) |719 734 (T) 698 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.010 * P=0.438N P=0.413N P=0.183 |P=0.167 P=0.580N P=0.554 P=0.294 | |POLY 3 | P=0.006 ** P=0.493N P=0.484N P=0.112 |P=0.159 P=0.588N P=0.545 P=0.276 | |POLY 1.5 | P=0.006 ** P=0.501N P=0.490N P=0.107 |P=0.164 P=0.596N P=0.543 P=0.280 | |POLY 6 | P=0.006 ** P=0.482N P=0.473N P=0.122 |P=0.154 P=0.577N P=0.553 P=0.274 | |LOGISTIC REGRESSION| P=0.010 * (e) (e) P=0.183 |P=0.154 P=0.559N P=0.557 P=0.287 | |COCH-ARM / FISHERS | P=0.008 ** P=0.512N P=0.494N P=0.101 |P=0.169 P=0.592N P=0.557 P=0.288 | |ORDER RESTRICTED | P=0.004 ** (e) (e) (e) |P=0.244 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Eye: Retina | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/44 (20%) 3/42 (7%) 3/45 (7%) 7/44 (16%) |4/43 (9%) 7/47 (15%) 11/47 (23%) 16/45 (36%) | |POLY-3 RATE (b) | 9/38.54 3/39.19 3/41.00 7/39.87 |4/39.95 7/44.51 11/43.41 16/42.06 | |POLY-3 PERCENT (g) | 23.4% 7.7% 7.3% 17.6% |10.0% 15.7% 25.3% 38.0% | |TERMINAL (d) | 6/22 (27%) 2/30 (7%) 2/34 (6%) 7/30 (23%) |3/32 (9%) 6/36 (17%) 8/35 (23%) 14/34 (41%) | |FIRST INCIDENCE | 623 697 722 733 (T) |719 625 657 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.376N P=0.026N* P=0.015N* P=0.188N |P<0.001 ** P=0.326 P=0.072 P=0.004 ** | |POLY 3 | P=0.508N P=0.052N P=0.043N* P=0.361N |P<0.001 ** P=0.325 P=0.060 P=0.002 ** | |POLY 1.5 | P=0.506N P=0.059N P=0.048N* P=0.376N |P<0.001 ** P=0.315 P=0.059 P=0.002 ** | |POLY 6 | P=0.511N P=0.042N* P=0.036N* P=0.337N |P<0.001 ** P=0.341 P=0.065 P=0.002 ** | |LOGISTIC REGRESSION| P=0.460N P=0.050N P=0.039N* P=0.299N |P<0.001 ** P=0.320 P=0.060 P=0.003 ** | |COCH-ARM / FISHERS | P=0.501N P=0.069N P=0.054N P=0.392N |P<0.001 ** P=0.315 P=0.064 P=0.003 ** | |ORDER RESTRICTED | P=0.080N (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Eye: Sclera | | Metaplasia Osseous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 0/47 (0%) 1/48 (2%) 1/47 (2%) |1/48 (2%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 2/42.07 0/42.07 1/43.02 1/43.09 |1/43.91 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 4.8% 0.0% 2.3% 2.3% |2.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 1/34 (3%) 0/30 (0%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 577 --- 733 (T) 505 |662 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.530N P=0.230N P=0.444N P=0.498N |P=0.340N P=0.490N P=0.495N P=0.515N | |POLY 3 | P=0.543N P=0.237N P=0.492N P=0.492N |P=0.330N P=0.497N P=0.501N P=0.506N | |POLY 1.5 | P=0.545N P=0.240N P=0.498N P=0.499N |P=0.330N P=0.500N P=0.503N P=0.504N | |POLY 6 | P=0.541N P=0.232N P=0.479N P=0.481N |P=0.331N P=0.492N P=0.498N P=0.507N | |LOGISTIC REGRESSION| P=0.549N P=0.246N P=0.495N P=0.494N |P=0.325N P=0.484N P=0.480N P=0.468N | |COCH-ARM / FISHERS | P=0.547N P=0.253N P=0.500N P=0.508N |P=0.330N P=0.500N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.264N (e) (e) (e) |P=0.126N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 16/48 (33%) 16/47 (34%) 16/48 (33%) 18/47 (38%) |19/48 (40%) 26/48 (54%) 22/48 (46%) 21/48 (44%) | |POLY-3 RATE (b) | 16/43.42 16/42.87 16/44.04 18/44.55 |19/43.99 26/45.82 22/44.14 21/44.47 | |POLY-3 PERCENT (g) | 36.9% 37.3% 36.3% 40.4% |43.2% 56.8% 49.8% 47.2% | |TERMINAL (d) | 9/24 (38%) 12/30 (40%) 14/34 (41%) 10/30 (33%) |17/33 (52%) 20/36 (56%) 19/35 (54%) 17/34 (50%) | |FIRST INCIDENCE | 564 615 477 505 |662 605 657 484 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.517N P=0.358N P=0.241N P=0.519N |P=0.502N P=0.210 P=0.432 P=0.450 | |POLY 3 | P=0.403 P=0.571 P=0.569N P=0.451 |P=0.494N P=0.138 P=0.338 P=0.433 | |POLY 1.5 | P=0.372 P=0.562 P=0.582N P=0.419 |P=0.493N P=0.115 P=0.322 P=0.422 | |POLY 6 | P=0.454 P=0.590N P=0.533N P=0.504 |P=0.488N P=0.179 P=0.376 P=0.457 | |LOGISTIC REGRESSION| P=0.360 P=0.577N P=0.568N P=0.377 |P=0.515 P=0.151 P=0.415 P=0.377 | |COCH-ARM / FISHERS | P=0.340 P=0.557 P=0.586N P=0.386 |P=0.488N P=0.110 P=0.340 P=0.418 | |ORDER RESTRICTED | P=0.569 (e) (e) (e) |P=0.351 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 37/48 (77%) 36/47 (77%) 40/48 (83%) 40/47 (85%) |35/48 (73%) 35/48 (73%) 33/48 (69%) 30/48 (63%) | |POLY-3 RATE (b) | 37/46.02 36/44.82 40/45.78 40/45.03 |35/46.34 35/45.82 33/45.13 30/46.00 | |POLY-3 PERCENT (g) | 80.4% 80.3% 87.4% 88.8% |75.5% 76.4% 73.1% 65.2% | |TERMINAL (d) | 19/24 (79%) 26/30 (87%) 32/34 (94%) 28/30 (93%) |25/33 (76%) 29/36 (81%) 25/35 (71%) 22/34 (65%) | |FIRST INCIDENCE | 541 567 477 601 |552 605 599 484 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.432N P=0.153N P=0.134N P=0.333N |P=0.183N P=0.364N P=0.307N P=0.218N | |POLY 3 | P=0.101 P=0.605N P=0.254 P=0.190 |P=0.116N P=0.559 P=0.491N P=0.190N | |POLY 1.5 | P=0.110 P=0.594N P=0.263 P=0.201 |P=0.117N P=0.544 P=0.489N P=0.195N | |POLY 6 | P=0.103 P=0.611N P=0.269 P=0.194 |P=0.108N P=0.585 P=0.463N P=0.178N | |LOGISTIC REGRESSION| P=0.170 P=0.524N P=0.311 P=0.302 |P=0.155N P=0.568N P=0.442N P=0.203N | |COCH-ARM / FISHERS | P=0.138 P=0.574N P=0.305 P=0.231 |P=0.123N P=0.591N P=0.411N P=0.191N | |ORDER RESTRICTED | P=0.186 (e) (e) (e) |P=0.183N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Heart: Atrium | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 2/47 (4%) 0/48 (0%) 3/47 (6%) |0/48 (0%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 1/41.52 2/42.24 0/43.02 3/42.55 |0/43.64 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 2.4% 4.7% 0.0% 7.1% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 2/30 (7%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 698 697 --- 698 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.295 P=0.550 P=0.461N P=0.364 |(e) (e) (e) (e) | |POLY 3 | P=0.269 P=0.506 P=0.493N P=0.314 |(e) (e) (e) (e) | |POLY 1.5 | P=0.264 P=0.499 P=0.497N P=0.306 |(e) (e) (e) (e) | |POLY 6 | P=0.277 P=0.518 P=0.484N P=0.326 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.271 P=0.502 P=0.499N P=0.322 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.259 P=0.492 P=0.500N P=0.301 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.192 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Intestine Large: Cecum, Lymphoid Tissue | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/47 (6%) 1/47 (2%) 0/47 (0%) 0/47 (0%) |0/47 (0%) 1/47 (2%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 3/40.90 1/42.07 0/42.06 0/42.42 |0/42.87 1/43.82 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 7.3% 2.4% 0.0% 0.0% |0.0% 2.3% 0.0% 0.0% | |TERMINAL (d) | 1/23 (4%) 1/30 (3%) 0/34 (0%) 0/30 (0%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 599 733 (T) --- --- |--- 725 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.039N* P=0.246N P=0.088N P=0.102N |P=0.499N P=0.528 (e) (e) | |POLY 3 | P=0.047N* P=0.295N P=0.113N P=0.112N |P=0.494N P=0.504 (e) (e) | |POLY 1.5 | P=0.048N* P=0.300N P=0.117N P=0.115N |P=0.497N P=0.501 (e) (e) | |POLY 6 | P=0.047N* P=0.285N P=0.106N P=0.106N |P=0.488N P=0.510 (e) (e) | |LOGISTIC REGRESSION| P=0.049N* P=0.306N P=0.121N P=0.127N |P=0.503N P=0.509 (e) (e) | |COCH-ARM / FISHERS | P=0.049N* P=0.308N P=0.121N P=0.121N |P=0.496N P=0.500 (e) (e) | |ORDER RESTRICTED | P=0.018N* (e) (e) (e) |P=0.386N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Intestine Large: Colon, Lymphoid Tissue | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 0/47 (0%) 2/47 (4%) 1/47 (2%) |0/47 (0%) 1/47 (2%) 1/48 (2%) 1/48 (2%) | |POLY-3 RATE (b) | 0/40.39 0/42.07 2/42.06 1/42.42 |0/42.87 1/43.82 1/43.67 1/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.8% 2.4% |0.0% 2.3% 2.3% 2.4% | |TERMINAL (d) | 0/23 (0%) 0/30 (0%) 2/34 (6%) 1/30 (3%) |0/33 (0%) 0/36 (0%) 1/35 (3%) 1/34 (3%) | |FIRST INCIDENCE | --- --- 733 (T) 733 (T) |--- 725 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.257 (e) P=0.328 P=0.553 |P=0.399 P=0.528 P=0.512 P=0.506 | |POLY 3 | P=0.235 (e) P=0.246 P=0.510 |P=0.394 P=0.504 P=0.504 P=0.499 | |POLY 1.5 | P=0.229 (e) P=0.241 P=0.505 |P=0.399 P=0.501 P=0.502 P=0.500 | |POLY 6 | P=0.243 (e) P=0.258 P=0.517 |P=0.391 P=0.510 P=0.508 P=0.498 | |LOGISTIC REGRESSION| (e) (e) P=0.328 P=0.553 |P=0.391 P=0.509 P=0.512 P=0.506 | |COCH-ARM / FISHERS | P=0.223 (e) P=0.247 P=0.500 |P=0.405 P=0.500 P=0.505 P=0.505 | |ORDER RESTRICTED | P=0.175 (e) (e) (e) |P=0.327 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Intestine Small: Ileum, Lymphoid Tissue | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/47 (9%) 1/45 (2%) 1/46 (2%) 3/46 (7%) |1/46 (2%) 2/48 (4%) 1/48 (2%) 0/48 (0%) | |POLY-3 RATE (b) | 4/40.39 1/40.70 1/41.84 3/42.08 |1/41.94 2/44.72 1/43.67 0/42.63 | |POLY-3 PERCENT (g) | 9.9% 2.5% 2.4% 7.1% |2.4% 4.5% 2.3% 0.0% | |TERMINAL (d) | 4/23 (17%) 1/30 (3%) 1/34 (3%) 2/30 (7%) |1/33 (3%) 1/36 (3%) 1/35 (3%) 0/34 (0%) | |FIRST INCIDENCE | 733 (T) 733 (T) 733 (T) 601 |734 (T) 725 734 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.477N P=0.106N P=0.080N P=0.373N |P=0.219N P=0.536 P=0.749N P=0.494N | |POLY 3 | P=0.555N P=0.175N P=0.167N P=0.478N |P=0.220N P=0.522 P=0.752N P=0.497N | |POLY 1.5 | P=0.558N P=0.183N P=0.176N P=0.494N |P=0.218N P=0.516 P=0.754N P=0.495N | |POLY 6 | P=0.552N P=0.162N P=0.151N P=0.451N |P=0.221N P=0.532 P=0.748N P=0.497N | |LOGISTIC REGRESSION| P=0.534N P=0.106N P=0.080N P=0.470N |P=0.220N P=0.542 P=0.749N (e) | |COCH-ARM / FISHERS | P=0.561N P=0.194N P=0.187N P=0.512N |P=0.213N P=0.516 P=0.742N P=0.489N | |ORDER RESTRICTED | P=0.186N (e) (e) (e) |P=0.236N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Intestine Small: Jejunum, Lymphoid Tissue | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/47 (2%) 0/45 (0%) 0/46 (0%) 2/46 (4%) |0/46 (0%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 1/40.39 0/40.70 0/41.84 2/41.67 |0/41.94 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 2.5% 0.0% 0.0% 4.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/23 (4%) 0/30 (0%) 0/34 (0%) 1/30 (3%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 733 (T) --- --- 724 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.250 P=0.447N P=0.422N P=0.577 |(e) (e) (e) (e) | |POLY 3 | P=0.224 P=0.498N P=0.493N P=0.511 |(e) (e) (e) (e) | |POLY 1.5 | P=0.223 P=0.503N P=0.499N P=0.502 |(e) (e) (e) (e) | |POLY 6 | P=0.225 P=0.490N P=0.482N P=0.525 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.240 (e) (e) P=0.554 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.223 P=0.511N P=0.505N P=0.492 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.137 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 0/48 (0%) 0/47 (0%) |47/48 (98%) 46/48 (96%) 47/48 (98%) 48/48 (100%) | |POLY-3 RATE (b) | 0/41.39 0/42.07 0/43.02 0/42.42 |47/48.00 46/46.90 47/48.00 48/48.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |97.9% 98.1% 97.9% 100.0% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |32/33 (97%) 36/36 (100%) 34/35 (97%) 34/34 (100%) | |FIRST INCIDENCE | --- --- --- --- |552 561 102 405 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.374 P=0.233N P=0.401N P=0.543 | |POLY 3 | (e) (e) (e) (e) |P=0.313 P=0.754 P=0.760 P=0.500 | |POLY 1.5 | (e) (e) (e) (e) |P=0.306 P=0.764 P=0.760 P=0.500 | |POLY 6 | (e) (e) (e) (e) |P=0.320 P=0.741 P=0.760 P=0.500 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.203 P=0.687N (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.220 P=0.500N P=0.753N P=0.500 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.316 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 43/48 (90%) 45/47 (96%) 46/48 (96%) 47/47 (100%)|34/48 (71%) 31/48 (65%) 27/48 (56%) 29/48 (60%) | |POLY-3 RATE (b) | 43/46.51 45/46.06 46/47.18 47/47.00 |34/45.24 31/45.42 27/44.31 29/43.22 | |POLY-3 PERCENT (g) | 92.5% 97.7% 97.5% 100.0% |75.2% 68.3% 60.9% 67.1% | |TERMINAL (d) | 23/24 (96%) 30/30 (100%) 34/34 (100%) 30/30 (100%)|27/33 (82%) 26/36 (72%) 23/35 (66%) 26/34 (77%) | |FIRST INCIDENCE | 541 567 435 475 |589 605 626 632 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.358N P=0.237N P=0.090N P=0.341N |P=0.173N P=0.169N P=0.060N P=0.152N | |POLY 3 | P=0.038 * P=0.214 P=0.233 P=0.056 |P=0.235N P=0.304N P=0.103N P=0.264N | |POLY 1.5 | P=0.028 * P=0.210 P=0.209 P=0.041 * |P=0.201N P=0.339N P=0.113N P=0.236N | |POLY 6 | P=0.073 P=0.248 P=0.322 P=0.100 |P=0.274N P=0.258N P=0.085N P=0.294N | |LOGISTIC REGRESSION| P=0.019 * P=0.242 P=0.164 P=0.038 * |P=0.235N P=0.206N P=0.066N P=0.221N | |COCH-ARM / FISHERS | P=0.027 * P=0.226 P=0.218 P=0.030 * |P=0.164N P=0.331N P=0.101N P=0.195N | |ORDER RESTRICTED | P=0.010 * (e) (e) (e) |P=0.192N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/48 (6%) 1/47 (2%) 1/48 (2%) 0/47 (0%) |2/48 (4%) 0/48 (0%) 0/48 (0%) 2/48 (4%) | |POLY-3 RATE (b) | 3/41.84 1/42.31 1/43.81 0/42.42 |2/44.25 0/44.68 0/43.67 2/42.85 | |POLY-3 PERCENT (g) | 7.2% 2.4% 2.3% 0.0% |4.5% 0.0% 0.0% 4.7% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 1/34 (3%) | |FIRST INCIDENCE | 662 667 439 --- |627 --- --- 676 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.076N P=0.268N P=0.263N P=0.110N |P=0.446 P=0.226N P=0.231N P=0.690 | |POLY 3 | P=0.082N P=0.301N P=0.289N P=0.116N |P=0.448 P=0.235N P=0.240N P=0.682 | |POLY 1.5 | P=0.083N P=0.307N P=0.297N P=0.119N |P=0.453 P=0.238N P=0.241N P=0.686 | |POLY 6 | P=0.081N P=0.290N P=0.274N P=0.111N |P=0.443 P=0.231N P=0.237N P=0.680 | |LOGISTIC REGRESSION| P=0.078N P=0.321N P=0.255N P=0.126N |P=0.463 P=0.207N P=0.201N P=0.667N | |COCH-ARM / FISHERS | P=0.084N P=0.316N P=0.308N P=0.125N |P=0.457 P=0.247N P=0.247N P=0.692N | |ORDER RESTRICTED | P=0.036N* (e) (e) (e) |P=0.257 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lacrimal Gland | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |3/10 (30%) 1/6 (17%) 0/8 (0%) 2/4 (50%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 0/0.00 0/0.00 |3/10.00 1/6.00 0/8.00 2/4.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |30.0% 16.7% 0.0% 50.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |3/10 (30%) 1/6 (17%) 0/8 (0%) 2/4 (50%) | |FIRST INCIDENCE | --- --- --- --- |734 (T) 734 (T) --- 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.507 P=0.500N P=0.151N P=0.466 | |POLY 3 | (e) (e) (e) (e) |P=0.507 P=0.500N P=0.138N P=0.467 | |POLY 1.5 | (e) (e) (e) (e) |P=0.507 P=0.500N P=0.138N P=0.467 | |POLY 6 | (e) (e) (e) (e) |P=0.507 P=0.500N P=0.138N P=0.467 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.507 P=0.500N (e) P=0.466 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.507 P=0.511N P=0.147N P=0.455 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.197 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lacrimal Gland | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |10/10 (100%) 6/6 (100%) 8/8 (100%) 4/4 (100%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 0/0.00 0/0.00 |10/10.00 6/6.00 8/8.00 4/4.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |100.0% 100.0% 100.0% 100.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) |10/10 (100%) 6/6 (100%) 8/8 (100%) 4/4 (100%) | |FIRST INCIDENCE | --- --- --- --- |734 (T) 734 (T) 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |(e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 2/47 (4%) 0/48 (0%) 2/47 (4%) |23/48 (48%) 30/48 (63%) 4/48 (8%) 1/48 (2%) | |POLY-3 RATE (b) | 0/41.39 2/42.48 0/43.02 2/42.52 |23/44.45 30/45.49 4/43.67 1/42.63 | |POLY-3 PERCENT (g) | 0.0% 4.7% 0.0% 4.7% |51.8% 66.0% 9.2% 2.4% | |TERMINAL (d) | 0/24 (0%) 1/30 (3%) 0/34 (0%) 1/30 (3%) |19/33 (58%) 25/36 (69%) 4/35 (11%) 1/34 (3%) | |FIRST INCIDENCE | --- 615 --- 707 |662 625 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.323 P=0.267 (e) P=0.283 |P<0.001N** P=0.230 P<0.001N** P<0.001N** | |POLY 3 | P=0.301 P=0.243 (e) P=0.243 |P<0.001N** P=0.119 P<0.001N** P<0.001N** | |POLY 1.5 | P=0.294 P=0.238 (e) P=0.238 |P<0.001N** P=0.104 P<0.001N** P<0.001N** | |POLY 6 | P=0.314 P=0.252 (e) P=0.251 |P<0.001N** P=0.145 P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P=0.285 P=0.223 (e) P=0.253 |P<0.001N** P=0.164 P<0.001N** P<0.001N** | |COCH-ARM / FISHERS | P=0.287 P=0.242 (e) P=0.242 |P<0.001N** P=0.109 P<0.001N** P<0.001N** | |ORDER RESTRICTED | P=0.121 (e) (e) (e) |P<0.001N** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/48 (8%) 18/47 (38%) 13/48 (27%) 19/47 (40%) |3/48 (6%) 2/48 (4%) 5/48 (10%) 3/48 (6%) | |POLY-3 RATE (b) | 4/41.95 18/43.47 13/43.84 19/43.58 |3/43.64 2/44.76 5/44.18 3/42.63 | |POLY-3 PERCENT (g) | 9.5% 41.4% 29.7% 43.6% |6.9% 4.5% 11.3% 7.0% | |TERMINAL (d) | 2/24 (8%) 13/30 (43%) 11/34 (32%) 14/30 (47%) |3/33 (9%) 1/36 (3%) 3/35 (9%) 3/34 (9%) | |FIRST INCIDENCE | 599 606 599 505 |734 (T) 714 657 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.026 * P=0.004 ** P=0.066 P=0.003 ** |P=0.441 P=0.461N P=0.394 P=0.650N | |POLY 3 | P=0.008 ** P<0.001 ** P=0.017 * P<0.001 ** |P=0.425 P=0.488N P=0.363 P=0.652 | |POLY 1.5 | P=0.006 ** P<0.001 ** P=0.015 * P<0.001 ** |P=0.436 P=0.498N P=0.354 P=0.654 | |POLY 6 | P=0.010 * P<0.001 ** P=0.022 * P<0.001 ** |P=0.416 P=0.475N P=0.380 P=0.652 | |LOGISTIC REGRESSION| P=0.009 ** P<0.001 ** P=0.019 * P<0.001 ** |P=0.429 P=0.460N P=0.355 P=0.650N | |COCH-ARM / FISHERS | P=0.007 ** P<0.001 ** P=0.015 * P<0.001 ** |P=0.450 P=0.500N P=0.357 P=0.661N | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P=0.422 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver | | Developmental Malformation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 1/47 (2%) 0/48 (0%) 1/47 (2%) |7/48 (15%) 5/48 (10%) 3/48 (6%) 5/48 (10%) | |POLY-3 RATE (b) | 1/41.93 1/42.44 0/43.02 1/43.09 |7/44.55 5/45.35 3/43.67 5/43.49 | |POLY-3 PERCENT (g) | 2.4% 2.4% 0.0% 2.3% |15.7% 11.0% 6.9% 11.5% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |2/33 (6%) 3/36 (8%) 3/35 (9%) 3/34 (9%) | |FIRST INCIDENCE | 564 629 --- 505 |662 625 734 (T) 585 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.596N P=0.758 P=0.513N P=0.751 |P=0.340N P=0.335N P=0.148N P=0.389N | |POLY 3 | P=0.599N P=0.758N P=0.495N P=0.755N |P=0.341N P=0.366N P=0.165N P=0.396N | |POLY 1.5 | P=0.601N P=0.759 P=0.498N P=0.759N |P=0.333N P=0.378N P=0.166N P=0.391N | |POLY 6 | P=0.596N P=0.751N P=0.487N P=0.747N |P=0.349N P=0.351N P=0.162N P=0.399N | |LOGISTIC REGRESSION| P=0.570N P=0.771N P=0.376N P=0.692N |P=0.318N P=0.374N P=0.160N P=0.358N | |COCH-ARM / FISHERS | P=0.603N P=0.747 P=0.500N P=0.747 |P=0.321N P=0.379N P=0.158N P=0.379N | |ORDER RESTRICTED | P=0.527N (e) (e) (e) |P=0.267N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/48 (6%) 14/47 (30%) 19/48 (40%) 33/47 (70%) |3/48 (6%) 12/48 (25%) 20/48 (42%) 16/48 (33%) | |POLY-3 RATE (b) | 3/41.39 14/42.52 19/43.16 33/44.83 |3/43.64 12/45.16 20/44.10 16/42.63 | |POLY-3 PERCENT (g) | 7.3% 32.9% 44.0% 73.6% |6.9% 26.6% 45.4% 37.5% | |TERMINAL (d) | 3/24 (13%) 12/30 (40%) 18/34 (53%) 23/30 (77%) |3/33 (9%) 10/36 (28%) 18/35 (51%) 16/34 (47%) | |FIRST INCIDENCE | 733 (T) 604 698 475 |734 (T) 605 657 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.011 * P<0.001 ** P<0.001 ** |P=0.002 ** P=0.020 * P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.012 * P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.011 * P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.014 * P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.006 ** P<0.001 ** P<0.001 ** |P<0.001 ** P=0.015 * P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** |P=0.003 ** P=0.011 * P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/47 (0%) 0/48 (0%) 0/47 (0%) |1/48 (2%) 1/48 (2%) 3/48 (6%) 1/48 (2%) | |POLY-3 RATE (b) | 1/41.39 0/42.07 0/43.02 0/42.42 |1/43.64 1/44.68 3/43.67 1/42.87 | |POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 0.0% |2.3% 2.2% 6.9% 2.3% | |TERMINAL (d) | 1/24 (4%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |1/33 (3%) 1/36 (3%) 3/35 (9%) 0/34 (0%) | |FIRST INCIDENCE | 733 (T) --- --- --- |734 (T) 734 (T) 734 (T) 669 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.304N P=0.455N P=0.431N P=0.455N |P=0.532 P=0.742N P=0.326 P=0.760N | |POLY 3 | P=0.338N P=0.497N P=0.492N P=0.495N |P=0.519 P=0.755N P=0.305 P=0.757 | |POLY 1.5 | P=0.335N P=0.500N P=0.497N P=0.499N |P=0.526 P=0.760N P=0.302 P=0.757 | |POLY 6 | P=0.343N P=0.490N P=0.483N P=0.488N |P=0.515 P=0.749N P=0.313 P=0.758 | |LOGISTIC REGRESSION| P=0.304N (e) (e) (e) |P=0.521 P=0.742N P=0.326 P=0.762N | |COCH-ARM / FISHERS | P=0.331N P=0.505N P=0.500N P=0.505N |P=0.535 P=0.753N P=0.308 P=0.753N | |ORDER RESTRICTED | P=0.115N (e) (e) (e) |P=0.436 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 2/47 (4%) 3/48 (6%) 0/47 (0%) |4/48 (8%) 1/48 (2%) 5/48 (10%) 1/48 (2%) | |POLY-3 RATE (b) | 2/41.39 2/42.48 3/43.14 0/42.42 |4/44.14 1/44.68 5/44.47 1/42.99 | |POLY-3 PERCENT (g) | 4.8% 4.7% 7.0% 0.0% |9.1% 2.2% 11.2% 2.3% | |TERMINAL (d) | 2/24 (8%) 1/30 (3%) 2/34 (6%) 0/30 (0%) |2/33 (6%) 1/36 (3%) 2/35 (6%) 0/34 (0%) | |FIRST INCIDENCE | 733 (T) 615 703 --- |662 734 (T) 599 633 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.160N P=0.631N P=0.643 P=0.190N |P=0.309N P=0.158N P=0.533 P=0.189N | |POLY 3 | P=0.193N P=0.685N P=0.519 P=0.231N |P=0.311N P=0.175N P=0.505 P=0.186N | |POLY 1.5 | P=0.198N P=0.693N P=0.508 P=0.236N |P=0.303N P=0.179N P=0.496 P=0.184N | |POLY 6 | P=0.185N P=0.671N P=0.542 P=0.224N |P=0.319N P=0.169N P=0.521 P=0.187N | |LOGISTIC REGRESSION| P=0.193N P=0.695 P=0.578 (e) |P=0.288N P=0.179N P=0.510 P=0.162N | |COCH-ARM / FISHERS | P=0.204N P=0.684 P=0.500 P=0.253N |P=0.294N P=0.181N P=0.500 P=0.181N | |ORDER RESTRICTED | P=0.160N (e) (e) (e) |P=0.150N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 0/48 (0%) 1/47 (2%) |2/48 (4%) 3/48 (6%) 7/48 (15%) 4/48 (8%) | |POLY-3 RATE (b) | 0/41.39 0/42.07 0/43.02 1/42.42 |2/43.64 3/44.69 7/43.67 4/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.4% |4.6% 6.7% 16.0% 9.4% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 1/30 (3%) |2/33 (6%) 2/36 (6%) 7/35 (20%) 4/34 (12%) | |FIRST INCIDENCE | --- --- --- 733 (T) |734 (T) 732 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.203 (e) (e) P=0.545 |P=0.226 P=0.542 P=0.092 P=0.350 | |POLY 3 | P=0.193 (e) (e) P=0.505 |P=0.207 P=0.511 P=0.078 P=0.326 | |POLY 1.5 | P=0.192 (e) (e) P=0.501 |P=0.216 P=0.502 P=0.076 P=0.329 | |POLY 6 | P=0.196 (e) (e) P=0.512 |P=0.199 P=0.524 P=0.083 P=0.325 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.545 |P=0.226 P=0.550 P=0.092 P=0.350 | |COCH-ARM / FISHERS | P=0.189 (e) (e) P=0.495 |P=0.229 P=0.500 P=0.079 P=0.339 | |ORDER RESTRICTED | P=0.125 (e) (e) (e) |P=0.147 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver | | Inflammation Granulomatous Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/48 (6%) 1/47 (2%) 1/48 (2%) 1/47 (2%) |10/48 (21%) 19/48 (40%) 20/48 (42%) 13/48 (27%) | |POLY-3 RATE (b) | 3/41.39 1/42.07 1/43.28 1/42.42 |10/43.97 19/46.62 20/43.93 13/42.85 | |POLY-3 PERCENT (g) | 7.3% 2.4% 2.3% 2.4% |22.7% 40.8% 45.5% 30.3% | |TERMINAL (d) | 3/24 (13%) 1/30 (3%) 0/34 (0%) 1/30 (3%) |8/33 (24%) 15/36 (42%) 17/35 (49%) 12/34 (35%) | |FIRST INCIDENCE | 733 (T) 733 (T) 662 733 (T) |662 60 709 676 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.215N P=0.227N P=0.209N P=0.227N |P=0.475 P=0.070 P=0.038 * P=0.339 | |POLY 3 | P=0.262N P=0.299N P=0.289N P=0.296N |P=0.408 P=0.051 P=0.018 * P=0.288 | |POLY 1.5 | P=0.265N P=0.306N P=0.299N P=0.304N |P=0.434 P=0.044 * P=0.018 * P=0.297 | |POLY 6 | P=0.259N P=0.287N P=0.270N P=0.283N |P=0.387 P=0.063 P=0.021 * P=0.283 | |LOGISTIC REGRESSION| P=0.244N P=0.227N P=0.280N P=0.227N |P=0.453 P=0.038 * P=0.029 * P=0.294 | |COCH-ARM / FISHERS | P=0.266N P=0.316N P=0.308N P=0.316N |P=0.485 P=0.037 * P=0.023 * P=0.317 | |ORDER RESTRICTED | P=0.176N (e) (e) (e) |P=0.083 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 24 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/47 (0%) 0/48 (0%) 2/47 (4%) |1/48 (2%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 1/41.77 0/42.07 0/43.02 2/42.42 |1/43.64 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 4.7% |2.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 2/30 (7%) |1/33 (3%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 623 --- --- 733 (T) |734 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.250 P=0.505N P=0.490N P=0.560 |P=0.329N P=0.483N P=0.488N P=0.494N | |POLY 3 | P=0.222 P=0.499N P=0.494N P=0.505 |P=0.331N P=0.495N P=0.500N P=0.505N | |POLY 1.5 | P=0.221 P=0.501N P=0.498N P=0.499 |P=0.330N P=0.499N P=0.502N P=0.503N | |POLY 6 | P=0.223 P=0.493N P=0.486N P=0.515 |P=0.333N P=0.490N P=0.495N P=0.505N | |LOGISTIC REGRESSION| P=0.219 P=0.506N P=0.464N P=0.490 |P=0.329N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.221 P=0.505N P=0.500N P=0.492 |P=0.330N P=0.500N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.134 (e) (e) (e) |P=0.125N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/47 (0%) 1/48 (2%) 0/47 (0%) |4/48 (8%) 2/48 (4%) 1/48 (2%) 3/48 (6%) | |POLY-3 RATE (b) | 1/41.39 0/42.07 1/43.02 0/42.42 |4/44.16 2/44.72 1/43.67 3/43.24 | |POLY-3 PERCENT (g) | 2.4% 0.0% 2.3% 0.0% |9.1% 4.5% 2.3% 6.9% | |TERMINAL (d) | 1/24 (4%) 0/30 (0%) 1/34 (3%) 0/30 (0%) |3/33 (9%) 1/36 (3%) 1/35 (3%) 2/34 (6%) | |FIRST INCIDENCE | 733 (T) --- 733 (T) --- |578 725 734 (T) 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.401N P=0.455N P=0.682N P=0.455N |P=0.476N P=0.304N P=0.170N P=0.497N | |POLY 3 | P=0.439N P=0.497N P=0.752N P=0.495N |P=0.481N P=0.331N P=0.182N P=0.511N | |POLY 1.5 | P=0.440N P=0.500N P=0.757N P=0.499N |P=0.477N P=0.338N P=0.184N P=0.508N | |POLY 6 | P=0.438N P=0.490N P=0.741N P=0.488N |P=0.485N P=0.320N P=0.176N P=0.511N | |LOGISTIC REGRESSION| P=0.401N (e) P=0.682N (e) |P=0.468N P=0.337N P=0.178N P=0.466N | |COCH-ARM / FISHERS | P=0.440N P=0.505N P=0.753N P=0.505N |P=0.471N P=0.339N P=0.181N P=0.500N | |ORDER RESTRICTED | P=0.246N (e) (e) (e) |P=0.291N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 25 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver | | Tension Lipidosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 0/48 (0%) 0/47 (0%) |1/48 (2%) 2/48 (4%) 0/48 (0%) 1/48 (2%) | |POLY-3 RATE (b) | 0/41.39 0/42.07 0/43.02 0/42.42 |1/43.64 2/44.68 0/43.67 1/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.3% 4.5% 0.0% 2.4% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |1/33 (3%) 2/36 (6%) 0/35 (0%) 1/34 (3%) | |FIRST INCIDENCE | --- --- --- --- |734 (T) 734 (T) --- 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.455N P=0.530 P=0.488N P=0.755N | |POLY 3 | (e) (e) (e) (e) |P=0.459N P=0.508 P=0.500N P=0.755 | |POLY 1.5 | (e) (e) (e) (e) |P=0.459N P=0.501 P=0.502N P=0.757 | |POLY 6 | (e) (e) (e) (e) |P=0.456N P=0.518 P=0.495N P=0.756 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.455N P=0.530 (e) P=0.755N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.456N P=0.500 P=0.500N P=0.753N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.391N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/48 (19%) 21/47 (45%) 10/48 (21%) 13/47 (28%) |5/48 (10%) 5/48 (10%) 17/48 (35%) 22/48 (46%) | |POLY-3 RATE (b) | 9/41.98 21/42.51 10/43.16 13/42.70 |5/44.45 5/44.76 17/44.13 22/42.85 | |POLY-3 PERCENT (g) | 21.4% 49.4% 23.2% 30.5% |11.3% 11.2% 38.5% 51.3% | |TERMINAL (d) | 5/24 (21%) 18/30 (60%) 9/34 (27%) 11/30 (37%) |2/33 (6%) 4/36 (11%) 16/35 (46%) 21/34 (62%) | |FIRST INCIDENCE | 613 620 698 687 |589 716 599 676 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.261N P=0.038 * P=0.413N P=0.413 |P<0.001 ** P=0.580N P=0.006 ** P<0.001 ** | |POLY 3 | P=0.410N P=0.005 ** P=0.527 P=0.241 |P<0.001 ** P=0.626N P=0.002 ** P<0.001 ** | |POLY 1.5 | P=0.435N P=0.005 ** P=0.509 P=0.229 |P<0.001 ** P=0.627 P=0.002 ** P<0.001 ** | |POLY 6 | P=0.369N P=0.005 ** P=0.566 P=0.264 |P<0.001 ** P=0.616N P=0.002 ** P<0.001 ** | |LOGISTIC REGRESSION| P=0.344N P=0.011 * P=0.593N P=0.304 |P<0.001 ** P=0.631 P=0.004 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.460N P=0.006 ** P=0.500 P=0.216 |P<0.001 ** P=0.630N P=0.003 ** P<0.001 ** | |ORDER RESTRICTED | P=0.147 (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 26 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver: Bile Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/47 (0%) 1/48 (2%) 0/47 (0%) |0/48 (0%) 0/48 (0%) 2/48 (4%) 0/48 (0%) | |POLY-3 RATE (b) | 1/41.39 0/42.07 1/43.02 0/42.42 |0/43.64 0/44.68 2/43.67 0/42.63 | |POLY-3 PERCENT (g) | 2.4% 0.0% 2.3% 0.0% |0.0% 0.0% 4.6% 0.0% | |TERMINAL (d) | 1/24 (4%) 0/30 (0%) 1/34 (3%) 0/30 (0%) |0/33 (0%) 0/36 (0%) 2/35 (6%) 0/34 (0%) | |FIRST INCIDENCE | 733 (T) --- 733 (T) --- |--- --- 734 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.401N P=0.455N P=0.682N P=0.455N |P=0.561 (e) P=0.251 (e) | |POLY 3 | P=0.439N P=0.497N P=0.752N P=0.495N |P=0.542 (e) P=0.237 (e) | |POLY 1.5 | P=0.440N P=0.500N P=0.757N P=0.499N |P=0.551 (e) P=0.235 (e) | |POLY 6 | P=0.438N P=0.490N P=0.741N P=0.488N |P=0.534 (e) P=0.242 (e) | |LOGISTIC REGRESSION| P=0.401N (e) P=0.682N (e) |(e) (e) P=0.251 (e) | |COCH-ARM / FISHERS | P=0.440N P=0.505N P=0.753N P=0.505N |P=0.561 (e) P=0.247 (e) | |ORDER RESTRICTED | P=0.246N (e) (e) (e) |P=0.247 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 41/48 (85%) 42/47 (89%) 42/48 (88%) 38/47 (81%) |16/48 (33%) 18/48 (38%) 19/48 (40%) 18/48 (38%) | |POLY-3 RATE (b) | 41/46.16 42/45.93 42/46.42 38/44.63 |16/44.57 18/45.42 19/44.27 18/43.16 | |POLY-3 PERCENT (g) | 88.8% 91.5% 90.5% 85.1% |35.9% 39.6% 42.9% 41.7% | |TERMINAL (d) | 22/24 (92%) 29/30 (97%) 33/34 (97%) 29/30 (97%) |12/33 (36%) 15/36 (42%) 17/35 (49%) 17/34 (50%) | |FIRST INCIDENCE | 541 487 435 601 |552 605 599 570 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.042N* P=0.198N P=0.050N P=0.054N |P=0.386 P=0.537 P=0.416 P=0.448 | |POLY 3 | P=0.263N P=0.468 P=0.534 P=0.410N |P=0.328 P=0.441 P=0.322 P=0.367 | |POLY 1.5 | P=0.253N P=0.431 P=0.503 P=0.401N |P=0.356 P=0.417 P=0.314 P=0.383 | |POLY 6 | P=0.260N P=0.535 P=0.621 P=0.407N |P=0.302 P=0.480 P=0.344 P=0.354 | |LOGISTIC REGRESSION| P=0.175N P=0.436 P=0.491 P=0.247N |P=0.333 P=0.444 P=0.344 P=0.377 | |COCH-ARM / FISHERS | P=0.226N P=0.395 P=0.500 P=0.375N |P=0.397 P=0.416 P=0.336 P=0.416 | |ORDER RESTRICTED | P=0.318N (e) (e) (e) |P=0.427 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 27 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Liver: Centrilobular | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 1/47 (2%) 1/48 (2%) 3/47 (6%) |0/48 (0%) 0/48 (0%) 1/48 (2%) 2/48 (4%) | |POLY-3 RATE (b) | 0/41.39 1/42.07 1/43.81 3/43.50 |0/43.64 0/44.68 1/43.77 2/43.23 | |POLY-3 PERCENT (g) | 0.0% 2.4% 2.3% 6.9% |0.0% 0.0% 2.3% 4.6% | |TERMINAL (d) | 0/24 (0%) 1/30 (3%) 0/34 (0%) 0/30 (0%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 733 (T) 439 505 |--- --- 709 633 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.065 P=0.545 P=0.496 P=0.134 |P=0.058 (e) P=0.516 P=0.234 | |POLY 3 | P=0.062 P=0.503 P=0.511 P=0.127 |P=0.061 (e) P=0.501 P=0.235 | |POLY 1.5 | P=0.059 P=0.500 P=0.505 P=0.122 |P=0.062 (e) P=0.498 P=0.235 | |POLY 6 | P=0.067 P=0.510 P=0.522 P=0.137 |P=0.061 (e) P=0.505 P=0.237 | |LOGISTIC REGRESSION| P=0.045 * P=0.545 (e) P=0.100 |P=0.064 (e) P=0.499 P=0.276 | |COCH-ARM / FISHERS | P=0.055 P=0.495 P=0.500 P=0.117 |P=0.064 (e) P=0.500 P=0.247 | |ORDER RESTRICTED | P=0.042 * (e) (e) (e) |P=0.073 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lung | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/47 (0%) 2/48 (4%) 0/47 (0%) |0/48 (0%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 1/41.51 0/42.07 2/43.31 0/42.42 |0/43.64 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 2.4% 0.0% 4.6% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 701 --- 668 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.477N P=0.476N P=0.578 P=0.482N |(e) (e) (e) (e) | |POLY 3 | P=0.496N P=0.497N P=0.515 P=0.496N |(e) (e) (e) (e) | |POLY 1.5 | P=0.499N P=0.501N P=0.506 P=0.500N |(e) (e) (e) (e) | |POLY 6 | P=0.492N P=0.491N P=0.532 P=0.489N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.505N P=0.502N P=0.500 P=0.503N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.503N P=0.505N P=0.500 P=0.505N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.321N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 28 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 2/47 (4%) 4/48 (8%) 6/47 (13%) |0/48 (0%) 3/48 (6%) 1/48 (2%) 2/48 (4%) | |POLY-3 RATE (b) | 2/41.99 2/42.07 4/43.02 6/42.74 |0/43.64 3/44.69 1/43.67 2/43.24 | |POLY-3 PERCENT (g) | 4.8% 4.8% 9.3% 14.0% |0.0% 6.7% 2.3% 4.6% | |TERMINAL (d) | 1/24 (4%) 2/30 (7%) 4/34 (12%) 5/30 (17%) |0/33 (0%) 2/36 (6%) 1/35 (3%) 1/34 (3%) | |FIRST INCIDENCE | 541 733 (T) 733 (T) 645 |--- 732 734 (T) 536 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.074 P=0.637N P=0.471 P=0.199 |P=0.391 P=0.141 P=0.512 P=0.238 | |POLY 3 | P=0.053 P=0.694N P=0.348 P=0.137 |P=0.389 P=0.123 P=0.500 P=0.235 | |POLY 1.5 | P=0.051 P=0.690 P=0.340 P=0.132 |P=0.388 P=0.119 P=0.498 P=0.235 | |POLY 6 | P=0.057 P=0.685N P=0.367 P=0.147 |P=0.393 P=0.128 P=0.505 P=0.236 | |LOGISTIC REGRESSION| P=0.054 P=0.678 P=0.340 P=0.125 |P=0.393 P=0.139 P=0.512 P=0.294 | |COCH-ARM / FISHERS | P=0.049 * P=0.684 P=0.339 P=0.127 |P=0.392 P=0.121 P=0.500 P=0.247 | |ORDER RESTRICTED | P=0.091 (e) (e) (e) |P=0.185 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lung: Alveolus | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/48 (6%) 4/47 (9%) 2/48 (4%) 4/47 (9%) |4/48 (8%) 3/48 (6%) 10/48 (21%) 6/48 (13%) | |POLY-3 RATE (b) | 3/41.77 4/42.12 2/43.02 4/42.48 |4/44.39 3/44.68 10/43.93 6/43.28 | |POLY-3 PERCENT (g) | 7.2% 9.5% 4.7% 9.4% |9.0% 6.7% 22.8% 13.9% | |TERMINAL (d) | 2/24 (8%) 2/30 (7%) 2/34 (6%) 3/30 (10%) |2/33 (6%) 3/36 (8%) 8/35 (23%) 4/34 (12%) | |FIRST INCIDENCE | 623 724 733 (T) 717 |589 734 (T) 676 633 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.573N P=0.601 P=0.371N P=0.599 |P=0.162 P=0.461N P=0.099 P=0.372 | |POLY 3 | P=0.510 P=0.505 P=0.487N P=0.509 |P=0.145 P=0.496N P=0.068 P=0.353 | |POLY 1.5 | P=0.502 P=0.496 P=0.495N P=0.499 |P=0.153 P=0.503N P=0.067 P=0.358 | |POLY 6 | P=0.524 P=0.520 P=0.468N P=0.525 |P=0.139 P=0.487N P=0.071 P=0.353 | |LOGISTIC REGRESSION| P=0.535 P=0.523 P=0.481N P=0.527 |P=0.156 P=0.499N P=0.072 P=0.384 | |COCH-ARM / FISHERS | P=0.493 P=0.488 P=0.500N P=0.488 |P=0.166 P=0.500N P=0.073 P=0.370 | |ORDER RESTRICTED | P=0.541 (e) (e) (e) |P=0.108 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 29 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 1/46 (2%) 2/48 (4%) 0/47 (0%) |1/46 (2%) 0/46 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 2/41.39 1/41.48 2/43.07 0/42.42 |1/42.22 0/42.97 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 4.8% 2.4% 4.6% 0.0% |2.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/24 (8%) 1/30 (3%) 1/34 (3%) 0/30 (0%) |1/32 (3%) 0/35 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 733 (T) 733 (T) 722 --- |734 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.174N P=0.422N P=0.569N P=0.190N |P=0.325N P=0.482N P=0.482N P=0.488N | |POLY 3 | P=0.209N P=0.499N P=0.680N P=0.231N |P=0.324N P=0.496N P=0.493N P=0.498N | |POLY 1.5 | P=0.212N P=0.507N P=0.688N P=0.236N |P=0.323N P=0.500N P=0.495N P=0.496N | |POLY 6 | P=0.205N P=0.486N P=0.662N P=0.224N |P=0.326N P=0.491N P=0.490N P=0.499N | |LOGISTIC REGRESSION| P=0.189N P=0.422N P=0.618N (e) |P=0.325N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.215N P=0.516N P=0.692N P=0.253N |P=0.324N P=0.500N P=0.489N P=0.489N | |ORDER RESTRICTED | P=0.151N (e) (e) (e) |P=0.118N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Mandibular | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/48 (6%) 5/46 (11%) 6/48 (13%) 4/47 (9%) |0/46 (0%) 0/46 (0%) 2/48 (4%) 2/48 (4%) | |POLY-3 RATE (b) | 3/41.39 5/41.48 6/43.16 4/42.48 |0/42.22 0/42.97 2/43.67 2/42.63 | |POLY-3 PERCENT (g) | 7.3% 12.1% 13.9% 9.4% |0.0% 0.0% 4.6% 4.7% | |TERMINAL (d) | 3/24 (13%) 5/30 (17%) 5/34 (15%) 3/30 (10%) |0/32 (0%) 0/35 (0%) 2/35 (6%) 2/34 (6%) | |FIRST INCIDENCE | 733 (T) 733 (T) 698 717 |--- --- 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.548N P=0.483 P=0.426 P=0.612 |P=0.078 (e) P=0.258 P=0.252 | |POLY 3 | P=0.506 P=0.357 P=0.262 P=0.514 |P=0.074 (e) P=0.245 P=0.239 | |POLY 1.5 | P=0.492 P=0.345 P=0.250 P=0.502 |P=0.077 (e) P=0.243 P=0.241 | |POLY 6 | P=0.529 P=0.378 P=0.288 P=0.534 |P=0.071 (e) P=0.249 P=0.238 | |LOGISTIC REGRESSION| P=0.534 P=0.483 P=0.343 P=0.570 |(e) (e) P=0.258 P=0.252 | |COCH-ARM / FISHERS | P=0.476 P=0.333 P=0.243 P=0.488 |P=0.082 (e) P=0.258 P=0.258 | |ORDER RESTRICTED | P=0.398 (e) (e) (e) |P=0.117 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 30 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 2/46 (4%) 3/48 (6%) 1/47 (2%) |1/46 (2%) 1/46 (2%) 4/48 (8%) 1/48 (2%) | |POLY-3 RATE (b) | 0/41.39 2/41.48 3/43.07 1/42.42 |1/42.22 1/43.97 4/44.39 1/42.63 | |POLY-3 PERCENT (g) | 0.0% 4.8% 7.0% 2.4% |2.4% 2.3% 9.0% 2.4% | |TERMINAL (d) | 0/24 (0%) 1/30 (3%) 2/34 (6%) 1/30 (3%) |1/32 (3%) 0/35 (0%) 3/35 (9%) 1/34 (3%) | |FIRST INCIDENCE | --- 732 722 733 (T) |734 (T) 60 482 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.517 P=0.289 P=0.187 P=0.545 |P=0.508 P=0.750N P=0.200 P=0.748N | |POLY 3 | P=0.486 P=0.237 P=0.125 P=0.505 |P=0.486 P=0.751N P=0.194 P=0.759N | |POLY 1.5 | P=0.475 P=0.233 P=0.121 P=0.501 |P=0.498 P=0.756N P=0.190 P=0.756N | |POLY 6 | P=0.504 P=0.246 P=0.135 P=0.512 |P=0.474 P=0.745N P=0.201 P=0.760N | |LOGISTIC REGRESSION| P=0.494 P=0.282 P=0.155 P=0.545 |P=0.539 P=0.563N P=0.204 P=0.748N | |COCH-ARM / FISHERS | P=0.462 P=0.237 P=0.121 P=0.495 |P=0.519 P=0.753N P=0.194 P=0.742N | |ORDER RESTRICTED | P=0.190 (e) (e) (e) |P=0.339 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Mandibular | | Infiltration Cellular Plasma Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/48 (10%) 6/46 (13%) 11/48 (23%) 7/47 (15%) |4/46 (9%) 8/46 (17%) 4/48 (8%) 0/48 (0%) | |POLY-3 RATE (b) | 5/41.49 6/41.88 11/43.32 7/42.62 |4/42.51 8/43.97 4/44.17 0/42.63 | |POLY-3 PERCENT (g) | 12.1% 14.3% 25.4% 16.4% |9.4% 18.2% 9.1% 0.0% | |TERMINAL (d) | 4/24 (17%) 3/30 (10%) 10/34 (29%) 6/30 (20%) |3/32 (9%) 7/35 (20%) 2/35 (6%) 0/34 (0%) | |FIRST INCIDENCE | 706 667 652 679 |653 60 599 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.386 P=0.611N P=0.244 P=0.529 |P=0.017N* P=0.219 P=0.601N P=0.061N | |POLY 3 | P=0.292 P=0.507 P=0.096 P=0.397 |P=0.016N* P=0.192 P=0.622N P=0.059N | |POLY 1.5 | P=0.279 P=0.489 P=0.088 P=0.381 |P=0.015N* P=0.185 P=0.627N P=0.058N | |POLY 6 | P=0.312 P=0.538 P=0.115 P=0.423 |P=0.017N* P=0.203 P=0.611N P=0.060N | |LOGISTIC REGRESSION| P=0.317 P=0.544 P=0.144 P=0.455 |P=0.013N* P=0.199 P=0.622N P=0.060N | |COCH-ARM / FISHERS | P=0.266 P=0.470 P=0.085 P=0.364 |P=0.015N* P=0.177 P=0.619N P=0.054N | |ORDER RESTRICTED | P=0.218 (e) (e) (e) |P=0.017N* (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 31 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 1/46 (2%) 1/48 (2%) 1/47 (2%) |1/46 (2%) 3/46 (7%) 0/48 (0%) 1/48 (2%) | |POLY-3 RATE (b) | 0/41.39 1/41.51 1/43.07 1/42.42 |1/42.22 3/42.97 0/43.67 1/42.63 | |POLY-3 PERCENT (g) | 0.0% 2.4% 2.3% 2.4% |2.4% 7.0% 0.0% 2.4% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 1/30 (3%) |1/32 (3%) 3/35 (9%) 0/35 (0%) 1/34 (3%) | |FIRST INCIDENCE | --- 724 722 733 (T) |734 (T) 734 (T) --- 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.424 P=0.546 P=0.557 P=0.545 |P=0.334N P=0.337 P=0.482N P=0.748N | |POLY 3 | P=0.414 P=0.501 P=0.508 P=0.505 |P=0.336N P=0.311 P=0.493N P=0.759N | |POLY 1.5 | P=0.407 P=0.496 P=0.503 P=0.501 |P=0.336N P=0.305 P=0.495N P=0.756N | |POLY 6 | P=0.426 P=0.509 P=0.518 P=0.512 |P=0.334N P=0.321 P=0.490N P=0.760N | |LOGISTIC REGRESSION| P=0.418 P=0.517 P=0.524 P=0.545 |P=0.334N P=0.337 (e) P=0.748N | |COCH-ARM / FISHERS | P=0.398 P=0.489 P=0.500 P=0.495 |P=0.331N P=0.308 P=0.489N P=0.742N | |ORDER RESTRICTED | P=0.331 (e) (e) (e) |P=0.266N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Mesenteric | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/48 (8%) 6/46 (13%) 6/48 (13%) 1/47 (2%) |2/46 (4%) 1/46 (2%) 4/48 (8%) 2/48 (4%) | |POLY-3 RATE (b) | 4/41.69 6/41.85 6/43.45 1/42.42 |2/42.22 1/42.97 4/43.89 2/42.63 | |POLY-3 PERCENT (g) | 9.6% 14.3% 13.8% 2.4% |4.7% 2.3% 9.1% 4.7% | |TERMINAL (d) | 2/24 (8%) 3/30 (10%) 4/34 (12%) 1/30 (3%) |2/32 (6%) 1/35 (3%) 3/35 (9%) 2/34 (6%) | |FIRST INCIDENCE | 659 667 652 733 (T) |734 (T) 734 (T) 676 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.076N P=0.493 P=0.546 P=0.134N |P=0.452 P=0.469N P=0.382 P=0.674N | |POLY 3 | P=0.099N P=0.371 P=0.395 P=0.173N |P=0.437 P=0.494N P=0.355 P=0.691N | |POLY 1.5 | P=0.105N P=0.357 P=0.380 P=0.179N |P=0.448 P=0.500N P=0.351 P=0.687N | |POLY 6 | P=0.091N P=0.396 P=0.427 P=0.163N |P=0.425 P=0.484N P=0.365 P=0.692N | |LOGISTIC REGRESSION| P=0.099N P=0.384 P=0.401 P=0.160N |P=0.436 P=0.469N P=0.360 P=0.674N | |COCH-ARM / FISHERS | P=0.112N P=0.343 P=0.370 P=0.187N |P=0.463 P=0.500N P=0.359 P=0.675N | |ORDER RESTRICTED | P=0.089N (e) (e) (e) |P=0.385 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 32 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Mesenteric | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 3/46 (7%) 2/48 (4%) 1/47 (2%) |0/46 (0%) 1/46 (2%) 0/48 (0%) 2/48 (4%) | |POLY-3 RATE (b) | 1/41.39 3/41.84 2/43.66 1/42.59 |0/42.22 1/42.97 0/43.67 2/42.64 | |POLY-3 PERCENT (g) | 2.4% 7.2% 4.6% 2.4% |0.0% 2.3% 0.0% 4.7% | |TERMINAL (d) | 0/24 (0%) 2/30 (7%) 0/34 (0%) 0/30 (0%) |0/32 (0%) 1/35 (3%) 0/35 (0%) 1/34 (3%) | |FIRST INCIDENCE | 732 629 543 687 |--- 734 (T) --- 733 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.396N P=0.368 P=0.563 P=0.730N |P=0.160 P=0.518 (e) P=0.253 | |POLY 3 | P=0.414N P=0.309 P=0.519 P=0.754N |P=0.158 P=0.504 (e) P=0.239 | |POLY 1.5 | P=0.424N P=0.300 P=0.508 P=0.760N |P=0.159 P=0.500 (e) P=0.242 | |POLY 6 | P=0.397N P=0.325 P=0.538 P=0.746N |P=0.157 P=0.509 (e) P=0.238 | |LOGISTIC REGRESSION| P=0.444N P=0.299 P=0.506 P=0.759N |P=0.157 P=0.518 (e) P=0.249 | |COCH-ARM / FISHERS | P=0.435N P=0.292 P=0.500 P=0.747 |P=0.163 P=0.500 (e) P=0.258 | |ORDER RESTRICTED | P=0.455N (e) (e) (e) |P=0.075 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/46 (0%) 1/48 (2%) 1/47 (2%) |1/46 (2%) 0/46 (0%) 2/48 (4%) 2/48 (4%) | |POLY-3 RATE (b) | 1/41.52 0/41.48 1/43.02 1/42.42 |1/42.22 0/42.97 2/43.89 2/42.63 | |POLY-3 PERCENT (g) | 2.4% 0.0% 2.3% 2.4% |2.4% 0.0% 4.6% 4.7% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 1/34 (3%) 1/30 (3%) |1/32 (3%) 0/35 (0%) 1/35 (3%) 2/34 (6%) | |FIRST INCIDENCE | 698 --- 733 (T) 733 (T) |734 (T) --- 676 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.537 P=0.482N P=0.699N P=0.725N |P=0.217 P=0.482N P=0.535 P=0.521 | |POLY 3 | P=0.505 P=0.500N P=0.753N P=0.756N |P=0.213 P=0.496N P=0.514 P=0.503 | |POLY 1.5 | P=0.502 P=0.504N P=0.758N P=0.760N |P=0.220 P=0.500N P=0.510 P=0.507 | |POLY 6 | P=0.507 P=0.493N P=0.743N P=0.749N |P=0.206 P=0.491N P=0.521 P=0.502 | |LOGISTIC REGRESSION| P=0.516 P=0.509N P=0.750N P=0.752N |P=0.213 (e) P=0.511 P=0.521 | |COCH-ARM / FISHERS | P=0.499 P=0.511N P=0.753N P=0.747 |P=0.227 P=0.500N P=0.516 P=0.516 | |ORDER RESTRICTED | P=0.543 (e) (e) (e) |P=0.270 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 33 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Mesenteric | | Infiltration Cellular Plasma Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 0/46 (0%) 0/48 (0%) 1/47 (2%) |0/46 (0%) 0/46 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 2/41.51 0/41.48 0/43.02 1/42.74 |0/42.22 0/42.97 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 4.8% 0.0% 0.0% 2.3% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/24 (4%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |0/32 (0%) 0/35 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 701 --- --- 645 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.464N P=0.203N P=0.181N P=0.447N |(e) (e) (e) (e) | |POLY 3 | P=0.506N P=0.237N P=0.229N P=0.490N |(e) (e) (e) (e) | |POLY 1.5 | P=0.503N P=0.242N P=0.234N P=0.498N |(e) (e) (e) (e) | |POLY 6 | P=0.510N P=0.229N P=0.219N P=0.477N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.503N P=0.227N P=0.218N P=0.514N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.500N P=0.258N P=0.247N P=0.508N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.124N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Pancreatic | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 1/46 (2%) 0/48 (0%) 0/47 (0%) |0/46 (0%) 1/46 (2%) 2/48 (4%) 1/48 (2%) | |POLY-3 RATE (b) | 1/41.39 1/41.48 0/43.02 0/42.42 |0/42.22 1/42.97 2/43.67 1/42.63 | |POLY-3 PERCENT (g) | 2.4% 2.4% 0.0% 0.0% |0.0% 2.3% 4.6% 2.4% | |TERMINAL (d) | 1/24 (4%) 1/30 (3%) 0/34 (0%) 0/30 (0%) |0/32 (0%) 1/35 (3%) 2/35 (6%) 1/34 (3%) | |FIRST INCIDENCE | 733 (T) 733 (T) --- --- |--- 734 (T) 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.188N P=0.712N P=0.431N P=0.455N |P=0.379 P=0.518 P=0.258 P=0.512 | |POLY 3 | P=0.217N P=0.760N P=0.492N P=0.495N |P=0.366 P=0.504 P=0.245 P=0.502 | |POLY 1.5 | P=0.219N P=0.756 P=0.497N P=0.499N |P=0.373 P=0.500 P=0.243 P=0.504 | |POLY 6 | P=0.214N P=0.752N P=0.483N P=0.488N |P=0.360 P=0.509 P=0.249 P=0.501 | |LOGISTIC REGRESSION| P=0.188N P=0.712N (e) (e) |(e) P=0.518 P=0.258 P=0.512 | |COCH-ARM / FISHERS | P=0.219N P=0.742 P=0.500N P=0.505N |P=0.384 P=0.500 P=0.258 P=0.511 | |ORDER RESTRICTED | P=0.246N (e) (e) (e) |P=0.233 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 34 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Renal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 2/46 (4%) 0/48 (0%) 0/47 (0%) |1/46 (2%) 0/46 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 1/41.39 2/41.49 0/43.02 0/42.42 |1/42.22 0/42.97 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 2.4% 4.8% 0.0% 0.0% |2.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 1/30 (3%) 0/34 (0%) 0/30 (0%) |1/32 (3%) 0/35 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 732 729 --- --- |734 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.133N P=0.578 P=0.439N P=0.464N |P=0.325N P=0.482N P=0.482N P=0.488N | |POLY 3 | P=0.149N P=0.501 P=0.492N P=0.495N |P=0.324N P=0.496N P=0.493N P=0.498N | |POLY 1.5 | P=0.152N P=0.493 P=0.497N P=0.500N |P=0.323N P=0.500N P=0.495N P=0.496N | |POLY 6 | P=0.143N P=0.515 P=0.483N P=0.488N |P=0.326N P=0.491N P=0.490N P=0.499N | |LOGISTIC REGRESSION| P=0.137N P=0.561 P=0.450N P=0.473N |P=0.325N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.155N P=0.484 P=0.500N P=0.505N |P=0.324N P=0.500N P=0.489N P=0.489N | |ORDER RESTRICTED | P=0.164N (e) (e) (e) |P=0.118N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Renal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 2/46 (4%) 0/48 (0%) 0/47 (0%) |2/46 (4%) 0/46 (0%) 1/48 (2%) 0/48 (0%) | |POLY-3 RATE (b) | 0/41.39 2/41.49 0/43.02 0/42.42 |2/42.22 0/42.97 1/43.67 0/42.63 | |POLY-3 PERCENT (g) | 0.0% 4.8% 0.0% 0.0% |4.7% 0.0% 2.3% 0.0% | |TERMINAL (d) | 0/24 (0%) 1/30 (3%) 0/34 (0%) 0/30 (0%) |2/32 (6%) 0/35 (0%) 1/35 (3%) 0/34 (0%) | |FIRST INCIDENCE | --- 729 --- --- |734 (T) --- 734 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.295N P=0.292 (e) (e) |P=0.214N P=0.219N P=0.469N P=0.225N | |POLY 3 | P=0.306N P=0.237 (e) (e) |P=0.221N P=0.233N P=0.488N P=0.235N | |POLY 1.5 | P=0.313N P=0.233 (e) (e) |P=0.217N P=0.237N P=0.491N P=0.233N | |POLY 6 | P=0.293N P=0.246 (e) (e) |P=0.226N P=0.227N P=0.482N P=0.235N | |LOGISTIC REGRESSION| P=0.302N P=0.273 (e) (e) |P=0.214N (e) P=0.469N (e) | |COCH-ARM / FISHERS | P=0.322N P=0.237 (e) (e) |P=0.213N P=0.247N P=0.484N P=0.237N | |ORDER RESTRICTED | P=0.242N (e) (e) (e) |P=0.073N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 35 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Mammary Gland | | Galactocele | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/43 (14%) 1/41 (2%) 6/46 (13%) 2/41 (5%) |7/48 (15%) 2/46 (4%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 6/37.86 1/36.69 6/41.16 2/37.52 |7/43.91 2/43.12 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 15.9% 2.7% 14.6% 5.3% |15.9% 4.6% 0.0% 0.0% | |TERMINAL (d) | 5/23 (22%) 1/28 (4%) 5/32 (16%) 2/29 (7%) |6/33 (18%) 1/34 (3%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 718 733 (T) 698 733 (T) |662 605 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.193N P=0.031N* P=0.393N P=0.074N |P=0.002N** P=0.076N P=0.008N** P=0.009N** | |POLY 3 | P=0.265N P=0.058N P=0.562N P=0.133N |P=0.002N** P=0.082N P=0.007N** P=0.008N** | |POLY 1.5 | P=0.273N P=0.061N P=0.572N P=0.140N |P=0.002N** P=0.088N P=0.008N** P=0.008N** | |POLY 6 | P=0.253N P=0.054N P=0.536N P=0.120N |P=0.002N** P=0.075N P=0.007N** P=0.008N** | |LOGISTIC REGRESSION| P=0.223N P=0.037N* P=0.470N P=0.088N |P=0.002N** P=0.091N P=0.008N** P=0.010N* | |COCH-ARM / FISHERS | P=0.284N P=0.062N P=0.572N P=0.148N |P=0.002N** P=0.090N P=0.006N** P=0.006N** | |ORDER RESTRICTED | P=0.094N (e) (e) (e) |P<0.001N** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/43 (12%) 4/41 (10%) 4/46 (9%) 5/41 (12%) |25/48 (52%) 20/46 (43%) 19/48 (40%) 22/48 (46%) | |POLY-3 RATE (b) | 5/38.15 4/36.69 4/41.02 5/37.59 |25/44.69 20/42.76 19/44.41 22/43.33 | |POLY-3 PERCENT (g) | 13.1% 10.9% 9.8% 13.3% |56.0% 46.8% 42.8% 50.8% | |TERMINAL (d) | 3/23 (13%) 4/28 (14%) 4/32 (13%) 4/29 (14%) |19/33 (58%) 19/34 (56%) 14/35 (40%) 20/34 (59%) | |FIRST INCIDENCE | 639 733 (T) 733 (T) 717 |589 716 657 632 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.492N P=0.395N P=0.321N P=0.502N |P=0.361N P=0.162N P=0.119N P=0.305N | |POLY 3 | P=0.529 P=0.525N P=0.454N P=0.623 |P=0.402N P=0.257N P=0.148N P=0.391N | |POLY 1.5 | P=0.519 P=0.529N P=0.460N P=0.611 |P=0.383N P=0.274N P=0.161N P=0.375N | |POLY 6 | P=0.547 P=0.513N P=0.437N P=0.622N |P=0.412N P=0.234N P=0.123N P=0.399N | |LOGISTIC REGRESSION| P=0.554N P=0.488N P=0.412N P=0.602N |P=0.429N P=0.164N P=0.129N P=0.381N | |COCH-ARM / FISHERS | P=0.511 P=0.531N P=0.457N P=0.600 |P=0.355N P=0.265N P=0.153N P=0.342N | |ORDER RESTRICTED | P=0.608 (e) (e) (e) |P=0.300N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 36 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Mammary Gland: Duct | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 12/43 (28%) 6/41 (15%) 3/46 (7%) 4/41 (10%) |10/48 (21%) 13/46 (28%) 7/48 (15%) 3/48 (6%) | |POLY-3 RATE (b) | 12/39.90 6/38.45 3/41.61 4/38.07 |10/43.91 13/43.99 7/43.89 3/42.99 | |POLY-3 PERCENT (g) | 30.1% 15.6% 7.2% 10.5% |22.8% 29.6% 16.0% 7.0% | |TERMINAL (d) | 5/23 (22%) 0/28 (0%) 1/32 (3%) 2/29 (7%) |9/33 (27%) 7/34 (21%) 6/35 (17%) 2/34 (6%) | |FIRST INCIDENCE | 577 567 599 658 |662 561 676 632 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.015N* P=0.080N P=0.006N** P=0.018N* |P=0.009N** P=0.371 P=0.249N P=0.034N* | |POLY 3 | P=0.018N* P=0.103N P=0.007N** P=0.029N* |P=0.007N** P=0.316 P=0.295N P=0.036N* | |POLY 1.5 | P=0.018N* P=0.108N P=0.007N** P=0.030N* |P=0.007N** P=0.289 P=0.305N P=0.036N* | |POLY 6 | P=0.017N* P=0.095N P=0.006N** P=0.027N* |P=0.008N** P=0.359 P=0.277N P=0.035N* | |LOGISTIC REGRESSION| P=0.020N* P=0.106N P=0.007N** P=0.038N* |P=0.008N** P=0.277 P=0.267N P=0.040N* | |COCH-ARM / FISHERS | P=0.019N* P=0.112N P=0.007N** P=0.032N* |P=0.007N** P=0.275 P=0.297N P=0.035N* | |ORDER RESTRICTED | P=0.006N** (e) (e) (e) |P=0.013N* (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Mesentery | | Accessory Spleen | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/5 (0%) 0/3 (0%) 2/6 (33%) 0/3 (0%) |0/8 (0%) 2/7 (29%) 0/1 (0%) 1/4 (25%) | |POLY-3 RATE (b) | 0/4.32 0/3.00 2/4.79 0/2.94 |0/5.94 2/7.00 0/1.00 1/3.78 | |POLY-3 PERCENT (g) | 0.0% 0.0% 41.7% 0.0% |0.0% 28.6% 0.0% 26.5% | |TERMINAL (d) | 0/2 (0%) 0/3 (0%) 2/2 (100%) 0/2 (0%) |0/2 (0%) 2/7 (29%) 0/1 (0%) 1/3 (33%) | |FIRST INCIDENCE | --- --- 733 (T) --- |--- 734 (T) --- 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.522 (e) P=0.193 (e) |P=0.495 P=0.540 (e) P=0.581 | |POLY 3 | P=0.579 (e) P=0.227 (e) |P=0.441 P=0.260 (e) P=0.402 | |POLY 1.5 | P=0.549 (e) P=0.237 (e) |P=0.401 P=0.224 (e) P=0.379 | |POLY 6 | P=0.621 (e) P=0.224 (e) |P=0.497 P=0.321 (e) P=0.439 | |LOGISTIC REGRESSION| (e) (e) P=0.193 (e) |(e) P=0.540 (e) P=0.581 | |COCH-ARM / FISHERS | P=0.511 (e) P=0.273 (e) |P=0.348 P=0.200 (e) P=0.333 | |ORDER RESTRICTED | P=0.249 (e) (e) (e) |P=0.229 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 37 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Mesentery | | Polyarteritis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/5 (0%) 0/3 (0%) 2/6 (33%) 1/3 (33%) |0/8 (0%) 0/7 (0%) 0/1 (0%) 0/4 (0%) | |POLY-3 RATE (b) | 0/4.32 0/3.00 2/5.06 1/2.94 |0/5.94 0/7.00 0/1.00 0/3.78 | |POLY-3 PERCENT (g) | 0.0% 0.0% 39.6% 34.1% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/2 (0%) 0/3 (0%) 1/2 (50%) 1/2 (50%) |0/2 (0%) 0/7 (0%) 0/1 (0%) 0/3 (0%) | |FIRST INCIDENCE | --- --- 662 733 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.188 (e) P=0.257 P=0.500 |(e) (e) (e) (e) | |POLY 3 | P=0.160 (e) P=0.244 P=0.417 |(e) (e) (e) (e) | |POLY 1.5 | P=0.152 (e) P=0.245 P=0.405 |(e) (e) (e) (e) | |POLY 6 | P=0.176 (e) P=0.258 P=0.440 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.144 (e) P=0.243 P=0.500 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.137 (e) P=0.273 P=0.375 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.186 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/5 (60%) 3/3 (100%) 2/6 (33%) 2/3 (67%) |6/8 (75%) 5/7 (71%) 1/1 (100%) 3/4 (75%) | |POLY-3 RATE (b) | 3/4.83 3/3.00 2/5.70 2/3.00 |6/6.91 5/7.00 1/1.00 3/4.00 | |POLY-3 PERCENT (g) | 62.1% 100.0% 35.1% 66.7% |86.8% 71.4% 100.0% 75.0% | |TERMINAL (d) | 1/2 (50%) 3/3 (100%) 0/2 (0%) 1/2 (50%) |2/2 (100%) 5/7 (71%) 1/1 (100%) 2/3 (67%) | |FIRST INCIDENCE | 662 733 (T) 435 717 |627 734 (T) 734 (T) 676 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.376N P=0.530N P=0.438N P=0.473N |P=0.151N P=0.038N* P=0.061N P=0.132N | |POLY 3 | P=0.454N P=0.363 P=0.404N P=0.713 |P=0.566N P=0.482N P=0.955 P=0.638N | |POLY 1.5 | P=0.457N P=0.352 P=0.401N P=0.701 |P=0.608N P=0.566N P=0.856 P=0.694N | |POLY 6 | P=0.448N P=0.384 P=0.408N P=0.733 |P=0.512N P=0.364N P=1.000 P=0.536N | |LOGISTIC REGRESSION| P=0.488N P=0.289 P=0.342N P=0.578 |P=0.475N P=0.187N P=0.061N P=0.423N | |COCH-ARM / FISHERS | P=0.459N P=0.357 P=0.392N P=0.714 |P=0.590 P=0.662N P=0.778 P=0.745N | |ORDER RESTRICTED | P=0.339N (e) (e) (e) |P=0.505N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 38 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Nose: Nasolacrimal Duct | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 10/48 (21%) 15/47 (32%) 16/48 (33%) 12/47 (26%) |21/48 (44%) 19/48 (40%) 18/48 (38%) 19/48 (40%) | |POLY-3 RATE (b) | 10/42.49 15/43.55 16/43.74 12/43.85 |21/44.96 19/44.96 18/45.23 19/42.91 | |POLY-3 PERCENT (g) | 23.5% 34.4% 36.6% 27.4% |46.7% 42.3% 39.8% 44.3% | |TERMINAL (d) | 5/24 (21%) 10/30 (33%) 14/34 (41%) 5/30 (17%) |15/33 (46%) 16/36 (44%) 15/35 (43%) 17/34 (50%) | |FIRST INCIDENCE | 577 620 599 505 |627 683 470 676 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.445N P=0.331 P=0.382 P=0.556 |P=0.412N P=0.300N P=0.280N P=0.391N | |POLY 3 | P=0.516 P=0.188 P=0.136 P=0.436 |P=0.469N P=0.416N P=0.326N P=0.494N | |POLY 1.5 | P=0.488 P=0.174 P=0.127 P=0.411 |P=0.439N P=0.430N P=0.342N P=0.465N | |POLY 6 | P=0.533N P=0.218 P=0.160 P=0.476 |P=0.502N P=0.397N P=0.307N P=0.526N | |LOGISTIC REGRESSION| P=0.480 P=0.173 P=0.153 P=0.385 |P=0.457N P=0.349N P=0.349N P=0.457N | |COCH-ARM / FISHERS | P=0.455 P=0.160 P=0.125 P=0.382 |P=0.398N P=0.418N P=0.339N P=0.418N | |ORDER RESTRICTED | P=0.277 (e) (e) (e) |P=0.515N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |6/48 (13%) 5/48 (10%) 10/48 (21%) 7/48 (15%) | |POLY-3 RATE (b) | |6/44.92 5/45.68 10/43.89 7/42.99 | |POLY-3 PERCENT (g) | |13.4% 11.0% 22.8% 16.3% | |TERMINAL (d) | |2/33 (6%) 4/36 (11%) 9/35 (26%) 6/34 (18%) | |FIRST INCIDENCE | |552 60 676 632 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.307 P=0.461N P=0.245 P=0.506 | |POLY 3 | |P=0.263 P=0.488N P=0.189 P=0.466 | |POLY 1.5 | |P=0.280 P=0.493N P=0.190 P=0.478 | |POLY 6 | |P=0.248 P=0.481N P=0.193 P=0.456 | |LOGISTIC REGRESSION| |P=0.322 P=0.466N P=0.203 P=0.512 | |COCH-ARM / FISHERS | |P=0.311 P=0.500N P=0.206 P=0.500 | |ORDER RESTRICTED | |P=0.272 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 39 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |8/48 (17%) 5/48 (10%) 10/48 (21%) 4/48 (8%) | |POLY-3 RATE (b) | |8/44.76 5/44.89 10/44.79 4/43.52 | |POLY-3 PERCENT (g) | |17.9% 11.1% 22.3% 9.2% | |TERMINAL (d) | |5/33 (15%) 3/36 (8%) 7/35 (20%) 2/34 (6%) | |FIRST INCIDENCE | |552 690 470 405 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.278N P=0.235N P=0.440 P=0.180N | |POLY 3 | |P=0.285N P=0.273N P=0.397 P=0.189N | |POLY 1.5 | |P=0.274N P=0.281N P=0.388 P=0.185N | |POLY 6 | |P=0.298N P=0.260N P=0.415 P=0.193N | |LOGISTIC REGRESSION| |P=0.255N P=0.274N P=0.409 P=0.135N | |COCH-ARM / FISHERS | |P=0.263N P=0.276N P=0.397 P=0.178N | |ORDER RESTRICTED | |P=0.200N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |3/48 (6%) 3/48 (6%) 3/48 (6%) 0/48 (0%) | |POLY-3 RATE (b) | |3/43.64 3/44.69 3/43.67 0/42.63 | |POLY-3 PERCENT (g) | |6.9% 6.7% 6.9% 0.0% | |TERMINAL (d) | |3/33 (9%) 2/36 (6%) 3/35 (9%) 0/34 (0%) | |FIRST INCIDENCE | |734 (T) 732 734 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.088N P=0.619N P=0.637N P=0.115N | |POLY 3 | |P=0.097N P=0.651N P=0.662N P=0.123N | |POLY 1.5 | |P=0.094N P=0.660N P=0.658 P=0.122N | |POLY 6 | |P=0.098N P=0.638N P=0.652N P=0.122N | |LOGISTIC REGRESSION| |P=0.088N P=0.614N P=0.637N (e) | |COCH-ARM / FISHERS | |P=0.090N P=0.661N P=0.661N P=0.121N | |ORDER RESTRICTED | |P=0.115N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 40 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Pancreas | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 2/47 (4%) 2/48 (4%) 1/47 (2%) |0/48 (0%) 2/48 (4%) 3/47 (6%) 1/48 (2%) | |POLY-3 RATE (b) | 1/41.39 2/42.07 2/43.02 1/42.42 |0/43.64 2/44.68 3/42.81 1/42.63 | |POLY-3 PERCENT (g) | 2.4% 4.8% 4.7% 2.4% |0.0% 4.5% 7.0% 2.4% | |TERMINAL (d) | 1/24 (4%) 2/30 (7%) 2/34 (6%) 1/30 (3%) |0/33 (0%) 2/36 (6%) 2/35 (6%) 1/34 (3%) | |FIRST INCIDENCE | 733 (T) 733 (T) 733 (T) 733 (T) |--- 734 (T) 724 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.473N P=0.578 P=0.621 P=0.712N |P=0.463 P=0.258 P=0.135 P=0.506 | |POLY 3 | P=0.524N P=0.506 P=0.514 P=0.755N |P=0.444 P=0.242 P=0.115 P=0.495 | |POLY 1.5 | P=0.532N P=0.499 P=0.505 P=0.760N |P=0.451 P=0.238 P=0.113 P=0.497 | |POLY 6 | P=0.512N P=0.517 P=0.530 P=0.748N |P=0.440 P=0.249 P=0.119 P=0.495 | |LOGISTIC REGRESSION| P=0.473N P=0.578 P=0.621 P=0.712N |P=0.451 P=0.258 P=0.127 P=0.506 | |COCH-ARM / FISHERS | P=0.541N P=0.492 P=0.500 P=0.747 |P=0.462 P=0.247 P=0.117 P=0.500 | |ORDER RESTRICTED | P=0.546N (e) (e) (e) |P=0.183 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 28/48 (58%) 16/47 (34%) 24/48 (50%) 22/47 (47%) |20/48 (42%) 16/48 (33%) 17/47 (36%) 18/48 (38%) | |POLY-3 RATE (b) | 28/45.72 16/43.24 24/44.15 22/45.08 |20/44.48 16/45.10 17/43.29 18/44.49 | |POLY-3 PERCENT (g) | 61.3% 37.0% 54.4% 48.8% |45.0% 35.5% 39.3% 40.5% | |TERMINAL (d) | 12/24 (50%) 11/30 (37%) 20/34 (59%) 14/30 (47%) |17/33 (52%) 14/36 (39%) 14/35 (40%) 13/34 (38%) | |FIRST INCIDENCE | 541 606 543 475 |589 625 657 484 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.221N P=0.007N** P=0.049N* P=0.073N |P=0.486N P=0.170N P=0.263N P=0.393N | |POLY 3 | P=0.389N P=0.016N* P=0.325N P=0.159N |P=0.490N P=0.240N P=0.372N P=0.414N | |POLY 1.5 | P=0.407N P=0.015N* P=0.307N P=0.167N |P=0.485N P=0.262N P=0.387N P=0.420N | |POLY 6 | P=0.372N P=0.017N* P=0.335N P=0.154N |P=0.487N P=0.211N P=0.339N P=0.397N | |LOGISTIC REGRESSION| P=0.422N P=0.015N* P=0.252N P=0.214N |P=0.529N P=0.204N P=0.335N P=0.446N | |COCH-ARM / FISHERS | P=0.435N P=0.015N* P=0.270N P=0.179N |P=0.478N P=0.264N P=0.368N P=0.417N | |ORDER RESTRICTED | P=0.118N (e) (e) (e) |P=0.414N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 41 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Pancreas: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 1/47 (2%) 2/48 (4%) 4/47 (9%) |0/48 (0%) 0/48 (0%) 0/47 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 0/41.39 1/42.07 2/43.02 4/43.14 |0/43.64 0/44.68 0/42.77 0/42.63 | |POLY-3 PERCENT (g) | 0.0% 2.4% 4.7% 9.3% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 1/30 (3%) 2/34 (6%) 3/30 (10%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 733 (T) 733 (T) 475 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.028 * P=0.545 P=0.318 P=0.086 |(e) (e) (e) (e) | |POLY 3 | P=0.024 * P=0.503 P=0.246 P=0.065 |(e) (e) (e) (e) | |POLY 1.5 | P=0.022 * P=0.500 P=0.241 P=0.062 |(e) (e) (e) (e) | |POLY 6 | P=0.026 * P=0.510 P=0.257 P=0.070 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.020 * P=0.545 P=0.318 P=0.051 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.021 * P=0.495 P=0.247 P=0.056 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.021 * (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Parathyroid Gland | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/38 (5%) 2/41 (5%) 0/40 (0%) 1/42 (2%) |0/42 (0%) 0/37 (0%) 0/40 (0%) 0/36 (0%) | |POLY-3 RATE (b) | 2/32.19 2/37.17 0/35.28 1/38.21 |0/38.18 0/35.00 0/36.55 0/31.77 | |POLY-3 PERCENT (g) | 6.2% 5.4% 0.0% 2.6% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/15 (7%) 1/27 (4%) 0/27 (0%) 1/28 (4%) |0/30 (0%) 0/29 (0%) 0/29 (0%) 0/25 (0%) | |FIRST INCIDENCE | 613 671 --- 733 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.204N P=0.578N P=0.177N P=0.356N |(e) (e) (e) (e) | |POLY 3 | P=0.250N P=0.642N P=0.216N P=0.440N |(e) (e) (e) (e) | |POLY 1.5 | P=0.253N P=0.654N P=0.222N P=0.452N |(e) (e) (e) (e) | |POLY 6 | P=0.245N P=0.620N P=0.204N P=0.421N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.256N P=0.683N P=0.227N P=0.471N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.255N P=0.663N P=0.234N P=0.462N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.218N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 42 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/45 (0%) 2/46 (4%) 1/48 (2%) 0/45 (0%) |3/47 (6%) 1/47 (2%) 1/45 (2%) 2/46 (4%) | |POLY-3 RATE (b) | 0/38.91 2/41.16 1/43.02 0/40.96 |3/43.48 1/43.68 1/41.91 2/40.63 | |POLY-3 PERCENT (g) | 0.0% 4.9% 2.3% 0.0% |6.9% 2.3% 2.4% 4.9% | |TERMINAL (d) | 0/23 (0%) 2/30 (7%) 1/34 (3%) 0/30 (0%) |2/33 (6%) 1/35 (3%) 1/35 (3%) 2/32 (6%) | |FIRST INCIDENCE | --- 733 (T) 733 (T) --- |589 734 (T) 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.348N P=0.298 P=0.578 (e) |P=0.519N P=0.289N P=0.291N P=0.515N | |POLY 3 | P=0.381N P=0.249 P=0.520 (e) |P=0.521N P=0.303N P=0.318N P=0.531N | |POLY 1.5 | P=0.390N P=0.246 P=0.516 (e) |P=0.516N P=0.308N P=0.321N P=0.523N | |POLY 6 | P=0.366N P=0.257 P=0.529 (e) |P=0.526N P=0.297N P=0.313N P=0.538N | |LOGISTIC REGRESSION| (e) P=0.298 P=0.578 (e) |P=0.518N P=0.300N P=0.321N P=0.512N | |COCH-ARM / FISHERS | P=0.399N P=0.253 P=0.516 (e) |P=0.511N P=0.308N P=0.325N P=0.510N | |ORDER RESTRICTED | P=0.326N (e) (e) (e) |P=0.313N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/45 (4%) 3/46 (7%) 5/48 (10%) 3/45 (7%) |8/47 (17%) 4/47 (9%) 6/45 (13%) 1/46 (2%) | |POLY-3 RATE (b) | 2/39.16 3/41.16 5/43.02 3/40.96 |8/43.35 4/44.07 6/42.57 1/40.63 | |POLY-3 PERCENT (g) | 5.1% 7.3% 11.6% 7.3% |18.5% 9.1% 14.1% 2.5% | |TERMINAL (d) | 1/23 (4%) 3/30 (10%) 5/34 (15%) 3/30 (10%) |6/33 (18%) 3/35 (9%) 4/35 (11%) 1/32 (3%) | |FIRST INCIDENCE | 666 733 (T) 733 (T) 733 (T) |653 625 626 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.503 P=0.606 P=0.380 P=0.606 |P=0.035N* P=0.156N P=0.351N P=0.021N* | |POLY 3 | P=0.426 P=0.523 P=0.255 P=0.521 |P=0.037N* P=0.168N P=0.400N P=0.020N* | |POLY 1.5 | P=0.413 P=0.516 P=0.247 P=0.511 |P=0.034N* P=0.176N P=0.411N P=0.019N* | |POLY 6 | P=0.446 P=0.535 P=0.272 P=0.537 |P=0.041N* P=0.156N P=0.380N P=0.020N* | |LOGISTIC REGRESSION| P=0.462 P=0.546 P=0.293 P=0.548 |P=0.033N* P=0.174N P=0.417N P=0.022N* | |COCH-ARM / FISHERS | P=0.399 P=0.511 P=0.245 P=0.500 |P=0.032N* P=0.177N P=0.421N P=0.016N* | |ORDER RESTRICTED | P=0.374 (e) (e) (e) |P=0.013N* (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 43 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/45 (2%) 7/46 (15%) 2/48 (4%) 7/45 (16%) |2/47 (4%) 4/47 (9%) 4/45 (9%) 5/46 (11%) | |POLY-3 RATE (b) | 1/38.91 7/41.67 2/43.02 7/41.83 |2/43.00 4/43.68 4/41.91 5/40.69 | |POLY-3 PERCENT (g) | 2.6% 16.8% 4.7% 16.7% |4.7% 9.2% 9.5% 12.3% | |TERMINAL (d) | 1/23 (4%) 5/30 (17%) 2/34 (6%) 3/30 (10%) |2/33 (6%) 4/35 (11%) 4/35 (11%) 4/32 (13%) | |FIRST INCIDENCE | 733 (T) 579 733 (T) 645 |734 (T) 734 (T) 734 (T) 719 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.169 P=0.065 P=0.636 P=0.064 |P=0.181 P=0.363 P=0.363 P=0.208 | |POLY 3 | P=0.126 P=0.036 * P=0.535 P=0.037 * |P=0.177 P=0.344 P=0.325 P=0.193 | |POLY 1.5 | P=0.115 P=0.034 * P=0.527 P=0.033 * |P=0.184 P=0.337 P=0.320 P=0.198 | |POLY 6 | P=0.146 P=0.041 * P=0.551 P=0.045 * |P=0.172 P=0.355 P=0.334 P=0.190 | |LOGISTIC REGRESSION| P=0.117 P=0.039 * P=0.636 P=0.033 * |P=0.169 P=0.363 P=0.363 P=0.192 | |COCH-ARM / FISHERS | P=0.108 P=0.031 * P=0.524 P=0.029 * |P=0.193 P=0.339 P=0.318 P=0.209 | |ORDER RESTRICTED | P=0.024 * (e) (e) (e) |P=0.173 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Preputial Gland | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/47 (0%) 0/48 (0%) 3/47 (6%) | | |POLY-3 RATE (b) | 1/41.39 0/42.07 0/43.02 3/42.55 | | |POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 7.1% | | |TERMINAL (d) | 1/24 (4%) 0/30 (0%) 0/34 (0%) 2/30 (7%) | | |FIRST INCIDENCE | 733 (T) --- --- 698 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.089 P=0.455N P=0.431N P=0.376 | | |POLY 3 | P=0.074 P=0.497N P=0.492N P=0.315 | | |POLY 1.5 | P=0.073 P=0.500N P=0.497N P=0.307 | | |POLY 6 | P=0.075 P=0.490N P=0.483N P=0.329 | | |LOGISTIC REGRESSION| P=0.082 (e) (e) P=0.339 | | |COCH-ARM / FISHERS | P=0.074 P=0.505N P=0.500N P=0.301 | | |ORDER RESTRICTED | P=0.041 * (e) (e) (e) | | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 44 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Preputial Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 1/47 (2%) 0/48 (0%) 3/47 (6%) | | |POLY-3 RATE (b) | 1/41.73 1/42.07 0/43.02 3/42.66 | | |POLY-3 PERCENT (g) | 2.4% 2.4% 0.0% 7.0% | | |TERMINAL (d) | 0/24 (0%) 1/30 (3%) 0/34 (0%) 1/30 (3%) | | |FIRST INCIDENCE | 639 733 (T) --- 698 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.190 P=0.739N P=0.485N P=0.362 | | |POLY 3 | P=0.163 P=0.759N P=0.494N P=0.313 | | |POLY 1.5 | P=0.161 P=0.759 P=0.498N P=0.306 | | |POLY 6 | P=0.167 P=0.753N P=0.486N P=0.325 | | |LOGISTIC REGRESSION| P=0.159 P=0.753 P=0.479N P=0.291 | | |COCH-ARM / FISHERS | P=0.159 P=0.747 P=0.500N P=0.301 | | |ORDER RESTRICTED | P=0.105 (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Preputial Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 35/48 (73%) 36/47 (77%) 38/48 (79%) 29/47 (62%) | | |POLY-3 RATE (b) | 35/45.84 36/44.91 38/47.00 29/45.38 | | |POLY-3 PERCENT (g) | 76.4% 80.2% 80.9% 63.9% | | |TERMINAL (d) | 17/24 (71%) 24/30 (80%) 28/34 (82%) 19/30 (63%) | | |FIRST INCIDENCE | 541 567 435 475 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.034N* P=0.269N P=0.192N P=0.053N | | |POLY 3 | P=0.062N P=0.424 P=0.389 P=0.136N | | |POLY 1.5 | P=0.077N P=0.423 P=0.355 P=0.151N | | |POLY 6 | P=0.048N* P=0.435 P=0.441 P=0.117N | | |LOGISTIC REGRESSION| P=0.092N P=0.477 P=0.321 P=0.165N | | |COCH-ARM / FISHERS | P=0.100N P=0.430 P=0.317 P=0.172N | | |ORDER RESTRICTED | P=0.059N (e) (e) (e) | | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 45 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Preputial Gland: Duct | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/48 (15%) 8/47 (17%) 11/48 (23%) 9/47 (19%) | | |POLY-3 RATE (b) | 7/41.83 8/42.07 11/43.02 9/42.52 | | |POLY-3 PERCENT (g) | 16.7% 19.0% 25.6% 21.2% | | |TERMINAL (d) | 5/24 (21%) 8/30 (27%) 11/34 (32%) 8/30 (27%) | | |FIRST INCIDENCE | 639 733 (T) 733 (T) 707 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.462 P=0.557N P=0.488 P=0.571 | | |POLY 3 | P=0.328 P=0.505 P=0.232 P=0.405 | | |POLY 1.5 | P=0.315 P=0.493 P=0.221 P=0.390 | | |POLY 6 | P=0.349 P=0.526 P=0.259 P=0.428 | | |LOGISTIC REGRESSION| P=0.381 P=0.583 P=0.333 P=0.473 | | |COCH-ARM / FISHERS | P=0.301 P=0.482 P=0.217 P=0.375 | | |ORDER RESTRICTED | P=0.358 (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Prostate | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 29/48 (60%) 21/47 (45%) 22/48 (46%) 18/47 (38%) | | |POLY-3 RATE (b) | 29/44.69 21/44.91 22/46.06 18/44.15 | | |POLY-3 PERCENT (g) | 64.9% 46.8% 47.8% 40.8% | | |TERMINAL (d) | 16/24 (67%) 13/30 (43%) 15/34 (44%) 13/30 (43%) | | |FIRST INCIDENCE | 564 487 435 505 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.016N* P=0.031N* P=0.017N* P=0.007N** | | |POLY 3 | P=0.033N* P=0.059N P=0.071N P=0.016N* | | |POLY 1.5 | P=0.036N* P=0.072N P=0.088N P=0.019N* | | |POLY 6 | P=0.030N* P=0.045N* P=0.050N P=0.012N* | | |LOGISTIC REGRESSION| P=0.043N* P=0.093N P=0.112N P=0.022N* | | |COCH-ARM / FISHERS | P=0.040N* P=0.092N P=0.110N P=0.025N* | | |ORDER RESTRICTED | P=0.013N* (e) (e) (e) | | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 46 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Prostate: Ventral | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 3/47 (6%) 1/48 (2%) 6/47 (13%) | | |POLY-3 RATE (b) | 1/41.39 3/42.07 1/43.02 6/42.93 | | |POLY-3 PERCENT (g) | 2.4% 7.1% 2.3% 14.0% | | |TERMINAL (d) | 1/24 (4%) 3/30 (10%) 1/34 (3%) 4/30 (13%) | | |FIRST INCIDENCE | 733 (T) 733 (T) 733 (T) 601 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.054 P=0.387 P=0.682N P=0.094 | | |POLY 3 | P=0.040 * P=0.311 P=0.752N P=0.061 | | |POLY 1.5 | P=0.038 * P=0.304 P=0.757N P=0.057 | | |POLY 6 | P=0.044 * P=0.323 P=0.741N P=0.068 | | |LOGISTIC REGRESSION| P=0.043 * P=0.387 P=0.682N P=0.062 | | |COCH-ARM / FISHERS | P=0.037 * P=0.301 P=0.753N P=0.052 | | |ORDER RESTRICTED | P=0.020 * (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Salivary Glands | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 1/48 (2%) 0/47 (0%) |2/48 (4%) 0/48 (0%) 0/48 (0%) 1/48 (2%) | |POLY-3 RATE (b) | 0/41.39 0/42.07 1/43.02 0/42.42 |2/44.02 0/44.68 0/43.67 1/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 0.0% |4.5% 0.0% 0.0% 2.4% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 1/34 (3%) 0/30 (0%) |1/33 (3%) 0/36 (0%) 0/35 (0%) 1/34 (3%) | |FIRST INCIDENCE | --- --- 733 (T) --- |627 --- --- 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.695 (e) P=0.569 (e) |P=0.501N P=0.230N P=0.236N P=0.496N | |POLY 3 | P=0.679 (e) P=0.508 (e) |P=0.503N P=0.234N P=0.239N P=0.511N | |POLY 1.5 | P=0.674 (e) P=0.503 (e) |P=0.500N P=0.237N P=0.240N P=0.508N | |POLY 6 | P=0.687 (e) P=0.517 (e) |P=0.506N P=0.229N P=0.235N P=0.513N | |LOGISTIC REGRESSION| (e) (e) P=0.569 (e) |P=0.497N P=0.227N P=0.224N P=0.495N | |COCH-ARM / FISHERS | P=0.667 (e) P=0.500 (e) |P=0.499N P=0.247N P=0.247N P=0.500N | |ORDER RESTRICTED | P=0.388 (e) (e) (e) |P=0.137N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 47 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Seminal Vesicle | | Decreased Secretory Fluid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 28/48 (58%) 31/47 (66%) 33/48 (69%) 36/47 (77%) | | |POLY-3 RATE (b) | 28/45.42 31/43.98 33/44.69 36/44.74 | | |POLY-3 PERCENT (g) | 61.6% 70.5% 73.8% 80.5% | | |TERMINAL (d) | 14/24 (58%) 22/30 (73%) 26/34 (77%) 24/30 (80%) | | |FIRST INCIDENCE | 541 606 599 601 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.304 P=0.438N P=0.359N P=0.393 | | |POLY 3 | P=0.030 * P=0.249 P=0.148 P=0.034 * | | |POLY 1.5 | P=0.031 * P=0.261 P=0.158 P=0.036 * | | |POLY 6 | P=0.034 * P=0.252 P=0.162 P=0.037 * | | |LOGISTIC REGRESSION| P=0.054 P=0.323 P=0.218 P=0.059 | | |COCH-ARM / FISHERS | P=0.040 * P=0.290 P=0.198 P=0.046 * | | |ORDER RESTRICTED | P=0.026 * (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Skin | | Cyst Epithelial Inclusion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 2/47 (4%) 0/47 (0%) 1/47 (2%) |0/48 (0%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 2/41.80 2/42.07 0/42.39 1/42.69 |0/43.64 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 4.8% 4.8% 0.0% 2.3% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/24 (4%) 2/30 (7%) 0/34 (0%) 0/30 (0%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 613 733 (T) --- 660 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.239N P=0.635N P=0.202N P=0.457N |(e) (e) (e) (e) | |POLY 3 | P=0.275N P=0.692N P=0.234N P=0.493N |(e) (e) (e) (e) | |POLY 1.5 | P=0.278N P=0.691 P=0.239N P=0.500N |(e) (e) (e) (e) | |POLY 6 | P=0.269N P=0.683N P=0.224N P=0.481N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.283N P=0.694 P=0.242N P=0.530N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.281N P=0.684 P=0.253N P=0.508N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.261N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 48 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Skin | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 1/47 (2%) 0/47 (0%) |2/48 (4%) 0/48 (0%) 1/48 (2%) 1/48 (2%) | |POLY-3 RATE (b) | 0/41.39 0/42.07 1/43.17 0/42.42 |2/43.64 0/44.68 1/43.67 1/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 0.0% |4.6% 0.0% 2.3% 2.4% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |2/33 (6%) 0/36 (0%) 1/35 (3%) 1/34 (3%) | |FIRST INCIDENCE | --- --- 439 --- |734 (T) --- 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.666 (e) P=0.496 (e) |P=0.544N P=0.219N P=0.479N P=0.490N | |POLY 3 | P=0.677 (e) P=0.508 (e) |P=0.553N P=0.232N P=0.500N P=0.508N | |POLY 1.5 | P=0.672 (e) P=0.502 (e) |P=0.548N P=0.236N P=0.504N P=0.506N | |POLY 6 | P=0.684 (e) P=0.520 (e) |P=0.559N P=0.225N P=0.492N P=0.508N | |LOGISTIC REGRESSION| P=0.999N (e) (e) (e) |P=0.544N (e) P=0.479N P=0.490N | |COCH-ARM / FISHERS | P=0.666 (e) P=0.495 (e) |P=0.543N P=0.247N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.389 (e) (e) (e) |P=0.276N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Skin: Epidermis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/47 (0%) 0/47 (0%) 1/47 (2%) |3/48 (6%) 1/48 (2%) 3/48 (6%) 3/48 (6%) | |POLY-3 RATE (b) | 1/41.39 0/42.07 0/42.39 1/42.42 |3/43.64 1/44.68 3/43.67 3/42.63 | |POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 2.4% |6.9% 2.2% 6.9% 7.0% | |TERMINAL (d) | 1/24 (4%) 0/30 (0%) 0/34 (0%) 1/30 (3%) |3/33 (9%) 1/36 (3%) 3/35 (9%) 3/34 (9%) | |FIRST INCIDENCE | 733 (T) --- --- 733 (T) |734 (T) 734 (T) 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.599 P=0.455N P=0.431N P=0.712N |P=0.415 P=0.274N P=0.637N P=0.650N | |POLY 3 | P=0.561 P=0.497N P=0.495N P=0.755N |P=0.396 P=0.297N P=0.662N P=0.652 | |POLY 1.5 | P=0.560 P=0.500N P=0.500N P=0.760N |P=0.406 P=0.304N P=0.658 P=0.654 | |POLY 6 | P=0.562 P=0.490N P=0.485N P=0.748N |P=0.388 P=0.286N P=0.652N P=0.652 | |LOGISTIC REGRESSION| P=0.599 (e) (e) P=0.712N |P=0.415 P=0.274N P=0.637N P=0.650N | |COCH-ARM / FISHERS | P=0.559 P=0.505N P=0.505N P=0.747 |P=0.416 P=0.308N P=0.661N P=0.661N | |ORDER RESTRICTED | P=0.393N (e) (e) (e) |P=0.489 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 49 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Skin: Epidermis | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 0/47 (0%) 1/47 (2%) |1/48 (2%) 1/48 (2%) 2/48 (4%) 3/48 (6%) | |POLY-3 RATE (b) | 0/41.39 0/42.07 0/42.39 1/42.42 |1/43.64 1/44.68 2/43.67 3/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.4% |2.3% 2.2% 4.6% 7.0% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 1/30 (3%) |1/33 (3%) 1/36 (3%) 2/35 (6%) 3/34 (9%) | |FIRST INCIDENCE | --- --- --- 733 (T) |734 (T) 734 (T) 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.203 (e) (e) P=0.545 |P=0.154 P=0.742N P=0.521 P=0.315 | |POLY 3 | P=0.194 (e) (e) P=0.505 |P=0.148 P=0.755N P=0.500 P=0.297 | |POLY 1.5 | P=0.192 (e) (e) P=0.501 |P=0.152 P=0.760N P=0.496 P=0.299 | |POLY 6 | P=0.197 (e) (e) P=0.512 |P=0.145 P=0.749N P=0.508 P=0.296 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.545 |P=0.154 P=0.742N P=0.521 P=0.315 | |COCH-ARM / FISHERS | P=0.189 (e) (e) P=0.495 |P=0.157 P=0.753N P=0.500 P=0.308 | |ORDER RESTRICTED | P=0.125 (e) (e) (e) |P=0.207 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Skin: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 0/47 (0%) 2/47 (4%) |0/48 (0%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 0/41.39 0/42.07 0/42.39 2/42.42 |0/43.64 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.7% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 2/30 (7%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- 733 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.049 * (e) (e) P=0.288 |(e) (e) (e) (e) | |POLY 3 | P=0.044 * (e) (e) P=0.242 |(e) (e) (e) (e) | |POLY 1.5 | P=0.043 * (e) (e) P=0.238 |(e) (e) (e) (e) | |POLY 6 | P=0.045 * (e) (e) P=0.250 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.288 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.043 * (e) (e) P=0.242 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.031 * (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 50 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/48 (10%) 6/47 (13%) 1/48 (2%) 5/47 (11%) |0/48 (0%) 0/48 (0%) 0/48 (0%) 1/48 (2%) | |POLY-3 RATE (b) | 5/41.39 6/42.07 1/43.02 5/42.42 |0/43.64 0/44.68 0/43.67 1/42.63 | |POLY-3 PERCENT (g) | 12.1% 14.3% 2.3% 11.8% |0.0% 0.0% 0.0% 2.4% | |TERMINAL (d) | 5/24 (21%) 6/30 (20%) 1/34 (3%) 5/30 (17%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 1/34 (3%) | |FIRST INCIDENCE | 733 (T) 733 (T) 733 (T) 733 (T) |--- --- --- 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.301N P=0.603N P=0.040N* P=0.485N |P=0.189 (e) (e) P=0.506 | |POLY 3 | P=0.400N P=0.512 P=0.092N P=0.616N |P=0.186 (e) (e) P=0.495 | |POLY 1.5 | P=0.410N P=0.498 P=0.097N P=0.629N |P=0.189 (e) (e) P=0.497 | |POLY 6 | P=0.384N P=0.535 P=0.081N P=0.594N |P=0.185 (e) (e) P=0.495 | |LOGISTIC REGRESSION| P=0.301N P=0.603N P=0.040N* P=0.485N |(e) (e) (e) P=0.506 | |COCH-ARM / FISHERS | P=0.419N P=0.485 P=0.102N P=0.616 |P=0.191 (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.277N (e) (e) (e) |P=0.116 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 3/47 (6%) 1/48 (2%) 8/47 (17%) |3/48 (6%) 4/48 (8%) 6/48 (13%) 5/48 (10%) | |POLY-3 RATE (b) | 2/41.39 3/42.10 1/43.75 8/43.50 |3/44.89 4/45.68 6/44.42 5/44.32 | |POLY-3 PERCENT (g) | 4.8% 7.1% 2.3% 18.4% |6.7% 8.8% 13.5% 11.3% | |TERMINAL (d) | 2/24 (8%) 2/30 (7%) 0/34 (0%) 5/30 (17%) |0/33 (0%) 1/36 (3%) 1/35 (3%) 2/34 (6%) | |FIRST INCIDENCE | 733 (T) 724 477 505 |578 605 657 405 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.026 * P=0.602 P=0.425N P=0.085 |P=0.265 P=0.527 P=0.279 P=0.352 | |POLY 3 | P=0.017 * P=0.508 P=0.481N P=0.052 |P=0.263 P=0.509 P=0.236 P=0.349 | |POLY 1.5 | P=0.016 * P=0.499 P=0.491N P=0.047 * |P=0.270 P=0.500 P=0.234 P=0.352 | |POLY 6 | P=0.019 * P=0.524 P=0.462N P=0.061 |P=0.255 P=0.523 P=0.245 P=0.348 | |LOGISTIC REGRESSION| P=0.015 * P=0.578 P=0.478N P=0.043 * |P=0.297 P=0.562 P=0.272 P=0.552 | |COCH-ARM / FISHERS | P=0.016 * P=0.490 P=0.500N P=0.042 * |P=0.276 P=0.500 P=0.243 P=0.357 | |ORDER RESTRICTED | P=0.013 * (e) (e) (e) |P=0.296 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 51 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 1/47 (2%) 2/48 (4%) 4/47 (9%) |0/48 (0%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 0/41.39 1/42.51 2/43.02 4/43.09 |0/43.64 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 0.0% 2.4% 4.7% 9.3% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 2/34 (6%) 3/30 (10%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 604 733 (T) 505 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.028 * P=0.505 P=0.318 P=0.085 |(e) (e) (e) (e) | |POLY 3 | P=0.023 * P=0.505 P=0.246 P=0.065 |(e) (e) (e) (e) | |POLY 1.5 | P=0.022 * P=0.501 P=0.241 P=0.062 |(e) (e) (e) (e) | |POLY 6 | P=0.025 * P=0.513 P=0.257 P=0.070 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.019 * P=0.506 P=0.318 P=0.053 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.021 * P=0.495 P=0.247 P=0.056 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.021 * (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 1/47 (2%) 0/48 (0%) 2/47 (4%) |0/48 (0%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 0/41.39 1/42.07 0/43.02 2/42.69 |0/43.64 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 0.0% 2.4% 0.0% 4.7% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 1/30 (3%) 0/34 (0%) 1/30 (3%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 733 (T) --- 660 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.178 P=0.545 (e) P=0.279 |(e) (e) (e) (e) | |POLY 3 | P=0.160 P=0.503 (e) P=0.244 |(e) (e) (e) (e) | |POLY 1.5 | P=0.156 P=0.500 (e) P=0.238 |(e) (e) (e) (e) | |POLY 6 | P=0.167 P=0.510 (e) P=0.253 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.156 P=0.545 (e) P=0.230 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.152 P=0.495 (e) P=0.242 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.078 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 52 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/48 (6%) 2/47 (4%) 0/48 (0%) 2/47 (4%) |1/48 (2%) 2/48 (4%) 3/48 (6%) 1/48 (2%) | |POLY-3 RATE (b) | 3/42.35 2/43.18 0/43.02 2/42.84 |1/43.87 2/45.24 3/44.41 1/42.99 | |POLY-3 PERCENT (g) | 7.1% 4.6% 0.0% 4.7% |2.3% 4.4% 6.8% 2.3% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |0/33 (0%) 1/36 (3%) 2/35 (6%) 0/34 (0%) | |FIRST INCIDENCE | 577 487 --- 676 |673 561 470 633 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.352N P=0.484N P=0.112N P=0.466N |P=0.576N P=0.524 P=0.325 P=0.755 | |POLY 3 | P=0.372N P=0.491N P=0.115N P=0.495N |P=0.581N P=0.511 P=0.310 P=0.756 | |POLY 1.5 | P=0.373N P=0.500N P=0.118N P=0.502N |P=0.576N P=0.503 P=0.305 P=0.757 | |POLY 6 | P=0.369N P=0.477N P=0.109N P=0.482N |P=0.584N P=0.521 P=0.318 P=0.757 | |LOGISTIC REGRESSION| P=0.369N P=0.539N P=0.098N P=0.546N |P=0.556N P=0.533 P=0.344 P=0.726N | |COCH-ARM / FISHERS | P=0.372N P=0.510N P=0.121N P=0.510N |P=0.567N P=0.500 P=0.308 P=0.753N | |ORDER RESTRICTED | P=0.211N (e) (e) (e) |P=0.464 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Stomach: Forestomach | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 1/47 (2%) 2/47 (4%) 0/47 (0%) |1/48 (2%) 0/48 (0%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 2/42.04 1/42.44 2/42.10 0/42.42 |1/43.70 0/44.68 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 4.8% 2.4% 4.8% 0.0% |2.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 1/34 (3%) 0/30 (0%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 564 629 722 --- |719 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.196N P=0.485N P=0.624N P=0.231N |P=0.329N P=0.484N P=0.489N P=0.494N | |POLY 3 | P=0.215N P=0.497N P=0.694N P=0.235N |P=0.331N P=0.496N P=0.500N P=0.505N | |POLY 1.5 | P=0.217N P=0.502N P=0.689 P=0.238N |P=0.330N P=0.499N P=0.502N P=0.504N | |POLY 6 | P=0.212N P=0.486N P=0.680N P=0.229N |P=0.333N P=0.490N P=0.496N P=0.505N | |LOGISTIC REGRESSION| P=0.224N P=0.523N P=0.687 P=0.248N |P=0.333N P=0.496N P=0.499N P=0.504N | |COCH-ARM / FISHERS | P=0.218N P=0.508N P=0.684 P=0.253N |P=0.330N P=0.500N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.153N (e) (e) (e) |P=0.125N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 53 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Stomach: Forestomach | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 1/47 (2%) 1/47 (2%) 2/47 (4%) |2/48 (4%) 0/48 (0%) 1/48 (2%) 1/48 (2%) | |POLY-3 RATE (b) | 2/41.84 1/42.46 1/42.06 2/42.42 |2/43.91 0/44.68 1/44.67 1/42.85 | |POLY-3 PERCENT (g) | 4.8% 2.4% 2.4% 4.7% |4.6% 0.0% 2.2% 2.3% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 1/34 (3%) 2/30 (7%) |1/33 (3%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 613 620 733 (T) 733 (T) |662 --- 102 676 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.577 P=0.480N P=0.434N P=0.640N |P=0.553N P=0.225N P=0.490N P=0.505N | |POLY 3 | P=0.536 P=0.495N P=0.498N P=0.689N |P=0.550N P=0.233N P=0.494N P=0.509N | |POLY 1.5 | P=0.533 P=0.501N P=0.504N P=0.693 |P=0.546N P=0.237N P=0.497N P=0.506N | |POLY 6 | P=0.540 P=0.484N P=0.484N P=0.680N |P=0.555N P=0.228N P=0.488N P=0.509N | |LOGISTIC REGRESSION| P=0.526 P=0.526N P=0.509N P=0.692 |P=0.545N P=0.235N P=0.261N P=0.487N | |COCH-ARM / FISHERS | P=0.531 P=0.508N P=0.508N P=0.684 |P=0.543N P=0.247N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.540N (e) (e) (e) |P=0.276N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Stomach: Forestomach, Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/47 (0%) 1/47 (2%) 2/47 (4%) |2/48 (4%) 0/48 (0%) 1/48 (2%) 0/48 (0%) | |POLY-3 RATE (b) | 1/41.39 0/42.07 1/42.06 2/42.42 |2/43.70 0/44.68 1/44.67 0/42.63 | |POLY-3 PERCENT (g) | 2.4% 0.0% 2.4% 4.7% |4.6% 0.0% 2.2% 0.0% | |TERMINAL (d) | 1/24 (4%) 0/30 (0%) 1/34 (3%) 2/30 (7%) |1/33 (3%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 733 (T) --- 733 (T) 733 (T) |719 --- 102 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.254 P=0.455N P=0.682N P=0.578 |P=0.223N P=0.221N P=0.487N P=0.233N | |POLY 3 | P=0.223 P=0.497N P=0.757N P=0.509 |P=0.229N P=0.232N P=0.492N P=0.243N | |POLY 1.5 | P=0.221 P=0.500N P=0.759 P=0.501 |P=0.225N P=0.236N P=0.497N P=0.241N | |POLY 6 | P=0.226 P=0.490N P=0.747N P=0.521 |P=0.234N P=0.226N P=0.485N P=0.243N | |LOGISTIC REGRESSION| P=0.254 (e) P=0.682N P=0.578 |P=0.204N P=0.223N P=0.287N P=0.241N | |COCH-ARM / FISHERS | P=0.217 P=0.505N P=0.747 P=0.492 |P=0.223N P=0.247N P=0.500N P=0.247N | |ORDER RESTRICTED | P=0.233 (e) (e) (e) |P=0.078N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 54 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Testes: Interstitial Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 17/48 (35%) 11/47 (23%) 5/48 (10%) 3/47 (6%) | | |POLY-3 RATE (b) | 17/44.78 11/42.92 5/44.60 3/43.46 | | |POLY-3 PERCENT (g) | 38.0% 25.6% 11.2% 6.9% | | |TERMINAL (d) | 3/24 (13%) 7/30 (23%) 3/34 (9%) 1/30 (3%) | | |FIRST INCIDENCE | 541 606 435 475 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001N** P=0.091N P=0.003N** P<0.001N** | | |POLY 3 | P<0.001N** P=0.154N P=0.002N** P<0.001N** | | |POLY 1.5 | P<0.001N** P=0.150N P=0.003N** P<0.001N** | | |POLY 6 | P<0.001N** P=0.162N P=0.002N** P<0.001N** | | |LOGISTIC REGRESSION| P<0.001N** P=0.157N P=0.003N** P<0.001N** | | |COCH-ARM / FISHERS | P<0.001N** P=0.145N P=0.003N** P<0.001N** | | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Testes: Seminiferous Tubule | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 11/48 (23%) 7/47 (15%) 3/48 (6%) 8/47 (17%) | | |POLY-3 RATE (b) | 11/42.84 7/42.07 3/43.48 8/42.52 | | |POLY-3 PERCENT (g) | 25.7% 16.6% 6.9% 18.8% | | |TERMINAL (d) | 6/24 (25%) 6/30 (20%) 2/34 (6%) 6/30 (20%) | | |FIRST INCIDENCE | 541 732 599 717 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.183N P=0.120N P=0.008N** P=0.189N | | |POLY 3 | P=0.264N P=0.225N P=0.017N* P=0.307N | | |POLY 1.5 | P=0.270N P=0.229N P=0.018N* P=0.316N | | |POLY 6 | P=0.253N P=0.214N P=0.013N* P=0.292N | | |LOGISTIC REGRESSION| P=0.250N P=0.205N P=0.022N* P=0.287N | | |COCH-ARM / FISHERS | P=0.277N P=0.231N P=0.020N* P=0.323N | | |ORDER RESTRICTED | P=0.082N (e) (e) (e) | | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 55 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Thymus | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/43 (0%) 0/42 (0%) 0/43 (0%) 0/42 (0%) |0/41 (0%) 2/47 (4%) 1/44 (2%) 1/42 (2%) | |POLY-3 RATE (b) | 0/37.12 0/38.28 0/38.32 0/38.00 |0/37.19 2/44.24 1/40.47 1/39.15 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 4.5% 2.5% 2.6% | |TERMINAL (d) | 0/21 (0%) 0/27 (0%) 0/30 (0%) 0/27 (0%) |0/28 (0%) 2/36 (6%) 1/33 (3%) 1/32 (3%) | |FIRST INCIDENCE | --- --- --- --- |--- 734 (T) 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.556 P=0.295 P=0.533 P=0.527 | |POLY 3 | (e) (e) (e) (e) |P=0.546 P=0.277 P=0.517 P=0.510 | |POLY 1.5 | (e) (e) (e) (e) |P=0.542 P=0.271 P=0.514 P=0.508 | |POLY 6 | (e) (e) (e) (e) |P=0.553 P=0.285 P=0.522 P=0.514 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) P=0.295 P=0.533 P=0.527 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.536 P=0.282 P=0.518 P=0.506 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.301 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/47 (17%) 6/47 (13%) 3/48 (6%) 3/46 (7%) |13/46 (28%) 5/46 (11%) 6/47 (13%) 1/48 (2%) | |POLY-3 RATE (b) | 8/41.00 6/42.08 3/43.16 3/41.55 |13/42.08 5/43.24 6/42.67 1/42.63 | |POLY-3 PERCENT (g) | 19.5% 14.3% 7.0% 7.2% |30.9% 11.6% 14.1% 2.4% | |TERMINAL (d) | 6/24 (25%) 5/30 (17%) 2/34 (6%) 3/30 (10%) |11/33 (33%) 5/35 (14%) 6/34 (18%) 1/34 (3%) | |FIRST INCIDENCE | 690 729 698 733 (T) |714 734 (T) 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.029N* P=0.235N P=0.035N* P=0.050N |P<0.001N** P=0.023N* P=0.052N P<0.001N** | |POLY 3 | P=0.051N P=0.365N P=0.081N P=0.091N |P<0.001N** P=0.025N* P=0.052N P<0.001N** | |POLY 1.5 | P=0.054N P=0.376N P=0.088N P=0.098N |P<0.001N** P=0.029N* P=0.056N P<0.001N** | |POLY 6 | P=0.046N* P=0.345N P=0.069N P=0.082N |P<0.001N** P=0.020N* P=0.047N* P<0.001N** | |LOGISTIC REGRESSION| P=0.038N* P=0.279N P=0.057N P=0.066N |P<0.001N** P=0.017N* P=0.041N* P<0.001N** | |COCH-ARM / FISHERS | P=0.057N P=0.387N P=0.093N P=0.106N |P<0.001N** P=0.032N* P=0.055N P<0.001N** | |ORDER RESTRICTED | P=0.060N (e) (e) (e) |P<0.001N** (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 56 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicle | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 0/47 (0%) 0/48 (0%) 3/46 (7%) |0/46 (0%) 1/46 (2%) 0/47 (0%) 2/48 (4%) | |POLY-3 RATE (b) | 0/40.80 0/42.07 0/43.02 3/41.82 |0/41.94 1/43.27 0/42.67 2/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 7.2% |0.0% 2.3% 0.0% 4.7% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 2/30 (7%) |0/33 (0%) 0/35 (0%) 0/34 (0%) 2/34 (6%) | |FIRST INCIDENCE | --- --- --- 661 |--- 725 --- 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.013 * (e) (e) P=0.157 |P=0.156 P=0.528 (e) P=0.245 | |POLY 3 | P=0.010 * (e) (e) P=0.122 |P=0.159 P=0.506 (e) P=0.241 | |POLY 1.5 | P=0.010 * (e) (e) P=0.119 |P=0.160 P=0.502 (e) P=0.242 | |POLY 6 | P=0.010 * (e) (e) P=0.129 |P=0.158 P=0.512 (e) P=0.240 | |LOGISTIC REGRESSION| P=0.011 * (e) (e) P=0.121 |P=0.150 P=0.511 (e) P=0.245 | |COCH-ARM / FISHERS | P=0.010 * (e) (e) P=0.117 |P=0.163 P=0.500 (e) P=0.258 | |ORDER RESTRICTED | P=0.009 ** (e) (e) (e) |P=0.076 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/47 (4%) 1/47 (2%) 3/48 (6%) 3/46 (7%) |1/46 (2%) 0/46 (0%) 0/47 (0%) 3/48 (6%) | |POLY-3 RATE (b) | 2/41.19 1/42.07 3/43.16 3/42.29 |1/41.94 0/43.24 0/42.67 3/42.63 | |POLY-3 PERCENT (g) | 4.9% 2.4% 7.0% 7.1% |2.4% 0.0% 0.0% 7.0% | |TERMINAL (d) | 1/24 (4%) 1/30 (3%) 2/34 (6%) 1/30 (3%) |1/33 (3%) 0/35 (0%) 0/34 (0%) 3/34 (9%) | |FIRST INCIDENCE | 623 733 (T) 698 505 |734 (T) --- --- 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.320 P=0.451N P=0.615 P=0.551 |P=0.076 P=0.488N P=0.494N P=0.315 | |POLY 3 | P=0.285 P=0.493N P=0.521 P=0.512 |P=0.076 P=0.494N P=0.497N P=0.311 | |POLY 1.5 | P=0.278 P=0.496N P=0.513 P=0.502 |P=0.079 P=0.498N P=0.498N P=0.314 | |POLY 6 | P=0.296 P=0.485N P=0.539 P=0.527 |P=0.074 P=0.488N P=0.493N P=0.309 | |LOGISTIC REGRESSION| P=0.261 P=0.502N P=0.515 P=0.464 |P=0.076 (e) (e) P=0.315 | |COCH-ARM / FISHERS | P=0.267 P=0.500N P=0.510 P=0.490 |P=0.082 P=0.500N P=0.495N P=0.325 | |ORDER RESTRICTED | P=0.383 (e) (e) (e) |P=0.039 * (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 57 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Urinary Bladder | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 0/48 (0%) 0/47 (0%) |0/47 (0%) 1/47 (2%) 1/48 (2%) 2/48 (4%) | |POLY-3 RATE (b) | 0/41.39 0/42.07 0/43.02 0/42.42 |0/42.70 1/43.85 1/43.67 2/42.63 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 2.3% 2.3% 4.7% | |TERMINAL (d) | 0/24 (0%) 0/30 (0%) 0/34 (0%) 0/30 (0%) |0/33 (0%) 1/36 (3%) 1/35 (3%) 2/34 (6%) | |FIRST INCIDENCE | --- --- --- --- |--- 734 (T) 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.158 P=0.517 P=0.512 P=0.245 | |POLY 3 | (e) (e) (e) (e) |P=0.159 P=0.505 P=0.504 P=0.237 | |POLY 1.5 | (e) (e) (e) (e) |P=0.162 P=0.501 P=0.502 P=0.238 | |POLY 6 | (e) (e) (e) (e) |P=0.158 P=0.512 P=0.509 P=0.236 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) P=0.517 P=0.512 P=0.245 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.165 P=0.500 P=0.505 P=0.253 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.117 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Urinary Bladder | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 1/47 (2%) 0/48 (0%) 0/47 (0%) |0/47 (0%) 2/47 (4%) 0/48 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 0/41.39 1/42.07 0/43.02 0/42.42 |0/42.70 2/43.96 0/43.67 0/42.63 | |POLY-3 PERCENT (g) | 0.0% 2.4% 0.0% 0.0% |0.0% 4.6% 0.0% 0.0% | |TERMINAL (d) | 0/24 (0%) 1/30 (3%) 0/34 (0%) 0/30 (0%) |0/33 (0%) 0/36 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 733 (T) --- --- |--- 709 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.474N P=0.545 (e) (e) |P=0.324N P=0.264 (e) (e) | |POLY 3 | P=0.494N P=0.503 (e) (e) |P=0.313N P=0.244 (e) (e) | |POLY 1.5 | P=0.498N P=0.500 (e) (e) |P=0.317N P=0.239 (e) (e) | |POLY 6 | P=0.485N P=0.510 (e) (e) |P=0.307N P=0.251 (e) (e) | |LOGISTIC REGRESSION| (e) P=0.545 (e) (e) |P=0.322N P=0.242 (e) (e) | |COCH-ARM / FISHERS | P=0.502N P=0.495 (e) (e) |P=0.317N P=0.247 (e) (e) | |ORDER RESTRICTED | P=0.379N (e) (e) (e) |P=0.253N (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 58 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Uterus: Cervix | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |5/48 (10%) 5/48 (10%) 2/48 (4%) 5/48 (10%) | |POLY-3 RATE (b) | |5/43.70 5/44.68 2/43.67 5/42.63 | |POLY-3 PERCENT (g) | |11.4% 11.2% 4.6% 11.7% | |TERMINAL (d) | |4/33 (12%) 5/36 (14%) 2/35 (6%) 5/34 (15%) | |FIRST INCIDENCE | |719 734 (T) 734 (T) 734 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.499N P=0.575N P=0.194N P=0.612N | |POLY 3 | |P=0.516N P=0.616N P=0.216N P=0.615 | |POLY 1.5 | |P=0.510N P=0.628N P=0.221N P=0.619 | |POLY 6 | |P=0.520N P=0.599N P=0.207N P=0.615 | |LOGISTIC REGRESSION| |P=0.511N P=0.565N P=0.190N P=0.629N | |COCH-ARM / FISHERS | |P=0.500N P=0.630N P=0.218N P=0.630N | |ORDER RESTRICTED | |P=0.477N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |3/48 (6%) 3/48 (6%) 4/48 (8%) 7/48 (15%) | |POLY-3 RATE (b) | |3/44.13 3/44.68 4/44.02 7/43.16 | |POLY-3 PERCENT (g) | |6.8% 6.7% 9.1% 16.2% | |TERMINAL (d) | |2/33 (6%) 3/36 (8%) 2/35 (6%) 6/34 (18%) | |FIRST INCIDENCE | |589 734 (T) 657 570 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.073 P=0.627N P=0.526 P=0.167 | |POLY 3 | |P=0.068 P=0.657N P=0.499 P=0.147 | |POLY 1.5 | |P=0.071 P=0.661 P=0.493 P=0.150 | |POLY 6 | |P=0.066 P=0.647N P=0.511 P=0.146 | |LOGISTIC REGRESSION| |P=0.072 P=0.663N P=0.503 P=0.158 | |COCH-ARM / FISHERS | |P=0.075 P=0.661N P=0.500 P=0.158 | |ORDER RESTRICTED | |P=0.103 (e) (e) (e) | |=================================================================================================================================| Date: 05/05/03 EXPERIMENT: 93029 TEST: 03 Page 59 Statistical Analysis of Non-neoplastic Lesions in Rats(F344/NCTR) - LEUKOMALACHITE GREEN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 PPM 91 PPM 272 PPM 543 PPM |0 PPM 91 PPM 272 PPM 543 PPM | | | | | |=================================================================================================================================| | | |Vagina | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |3/48 (6%) 2/48 (4%) 1/48 (2%) 2/48 (4%) | |POLY-3 RATE (b) | |3/44.24 2/44.68 1/43.67 2/43.19 | |POLY-3 PERCENT (g) | |6.8% 4.5% 2.3% 4.6% | |TERMINAL (d) | |0/33 (0%) 2/36 (6%) 1/35 (3%) 0/34 (0%) | |FIRST INCIDENCE | |662 734 (T) 734 (T) 585 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.420N P=0.471N P=0.296N P=0.515N | |POLY 3 | |P=0.416N P=0.495N P=0.310N P=0.511N | |POLY 1.5 | |P=0.412N P=0.501N P=0.312N P=0.508N | |POLY 6 | |P=0.419N P=0.488N P=0.306N P=0.513N | |LOGISTIC REGRESSION| |P=0.401N P=0.499N P=0.298N P=0.445N | |COCH-ARM / FISHERS | |P=0.406N P=0.500N P=0.308N P=0.500N | |ORDER RESTRICTED | |P=0.364N (e) (e) (e) | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Number of tumor-bearing animals / Poly-3 number (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers exact tests compare directly the overall incidence rates For all tests a negative trend is indicated by N (e) Value of Statistic cannot be computed. (g) Poly-3 adjusted lifetime tumor incidence. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).