TDMS Study 92012-05 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst 2-METHYLIMIDAZOLE DATE: 03/14/03 EXPERIMENT: 92012 TEST: 05 TIME: 10:41:17 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-85420 ROUTE: DOSED FEED NTP C#: 92012B PATHOLOGIST: FARNELL, DANIEL R. CAS: 693-98-1 ------------------------------------------------------------------------------------------------------------------------------------ FINAL#1; REVISION#1 REASONS FOR REMOVAL: 25019 Moribund Sacrifice 25020 Natural Death 25021 Terminal Sacrifice REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst 2-METHYLIMIDAZOLE DATE: 03/14/03 EXPERIMENT: 92012 TEST: 05 TIME: 10:41:17 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-85420 ROUTE: DOSED FEED NTP C#: 92012B PATHOLOGIST: FARNELL, DANIEL R. CAS: 693-98-1 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF 2-METHYLIMIDAZOLE =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Accessory Adrenal Cortical Nodule Hemorrhage Bone Marrow: Myeloid Cell Hyperplasia Harderian Gland: Epithelium Hyperplasia Focal Heart Cardiomyopathy Liver Basophilic Focus Hematopoietic Cell Proliferation Infiltration Cellular Mixed Cell Inflammation Granulomatous Mixed Cell Focus Liver: Hepatocyte, Centrilobular Vacuolization Cytoplasmic Lung Hyperplasia Focal Histiocytic Metaplasia Osseous Lung: Alveolar Epithelium Hyperplasia Focal Lymph Node: Pancreatic Hemorrhage Hyperplasia Mammary Gland Dilatation Hyperplasia Mesentery Hemorrhage Mesentery: Fat Necrosis Focal Nose: Nasolacrimal Duct Inflammation Pancreas: Acinus Atrophy Focal Pancreas: Duct Cyst Focal Preputial Gland Degeneration Cystic Inflammation Chronic Spleen Inflammation Granulomatous Stomach, Forestomach: Epithelium Hyperplasia Stomach, Glandular Erosion Ulcer Testes Atrophy Testes: Bilateral, Interstitial Cell Hyperplasia Focal Testes: Interstitial Cell Hyperplasia Focal Thyroid Gland: C-Cell Hyperplasia Thyroid Gland: Follicular Cell Hyperplasia =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Bone Marrow Hyperplasia Focal Histiocytic Clitoral Gland Degeneration Cystic Kidney Nephropathy Kidney: Renal Tubule Accumulation, Hyaline Droplet Pigmentation Liver Basophilic Focus Hepatodiaphragmatic Nodule Infarct Infiltration Cellular Mixed Cell NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst 2-METHYLIMIDAZOLE DATE: 03/14/03 EXPERIMENT: 92012 TEST: 05 TIME: 10:41:17 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-85420 ROUTE: DOSED FEED NTP C#: 92012B PATHOLOGIST: FARNELL, DANIEL R. CAS: 693-98-1 Inflammation Granulomatous Mixed Cell Focus Liver: Bile Duct Hyperplasia Lung Hyperplasia Infiltration Cellular Mixed Cell Lymph Node, Mesenteric Ectasia Pigmentation Lymph Node: Mediastinal Hemorrhage Lymph Node: Pancreatic Ectasia Hyperplasia Pigmentation Mammary Gland Dilatation Mesentery: Fat Necrosis Focal Nose: Nasolacrimal Duct Inflammation Ovary Cyst Pituitary Gland: Pars Distalis Degeneration Cystic Focal Hemorrhage Focal Pituitary Gland: Pars Intermedia Cyst Pituitary Gland: Rathke's Cleft Hemorrhage Salivary Glands: Duct Mineralization Focal Skin Necrosis Focal Spleen Inflammation Granulomatous Stomach, Glandular: Glands Hyperplasia Focal Thyroid Gland: C-Cell Hyperplasia Thyroid Gland: Follicle Mineralization Focal Thyroid Gland: Follicular Cell Hyperplasia Urinary Bladder: Transitional Epithelium Hyperplasia Uterus: Endometrium Hyperplasia Cystic =============================================================== Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Accessory Adrenal Cortical Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 4/50 (8%) 9/50 (18%) 5/50 (10%) |2/50 (4%) 2/49 (4%) 5/50 (10%) 5/50 (10%) | |POLY-3 RATE (b) | 1/46.41 4/45.93 9/44.49 5/44.51 |2/46.00 2/44.59 5/43.58 5/48.02 | |POLY-3 PERCENT (g) | 2.2% 8.7% 20.2% 11.2% |4.4% 4.5% 11.5% 10.4% | |TERMINAL (d) | 0/35 (0%) 4/40 (10%) 9/36 (25%) 3/35 (9%) |2/40 (5%) 2/39 (5%) 1/28 (4%) 5/42 (12%) | |FIRST INCIDENCE | 651 729 (T) 729 (T) 598 |729 (T) 729 (T) 244 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.187 P=0.213 P=0.011 * P=0.101 |P=0.124 P=0.686 P=0.156 P=0.236 | |POLY 3 | P=0.186 P=0.175 P=0.006 ** P=0.092 |P=0.124 P=0.683 P=0.194 P=0.234 | |POLY 1.5 | P=0.195 P=0.178 P=0.007 ** P=0.095 |P=0.118 P=0.684 P=0.205 P=0.228 | |POLY 6 | P=0.181 P=0.174 P=0.006 ** P=0.090 |P=0.131 P=0.683 P=0.179 P=0.243 | |LOGISTIC REGRESSION| P=0.189 P=0.178 P=0.008 ** P=0.107 |P=0.076 P=0.686 P=0.421 P=0.236 | |COCH-ARM / FISHERS | P=0.218 P=0.181 P=0.008 ** P=0.102 |P=0.108 P=0.684 P=0.218 P=0.218 | |ORDER RESTRICTED | P=0.021 * (e) (e) (e) |P=0.174 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 1/49 (2%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 0/43.91 |1/46.00 1/44.92 1/41.10 2/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.2% 2.2% 2.4% 4.2% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |1/40 (3%) 0/39 (0%) 0/28 (0%) 2/42 (5%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 638 638 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.371 P=0.757 P=0.707 P=0.517 | |POLY 3 | (e) (e) (e) (e) |P=0.365 P=0.755 P=0.735 P=0.515 | |POLY 1.5 | (e) (e) (e) (e) |P=0.359 P=0.755 P=0.745 P=0.509 | |POLY 6 | (e) (e) (e) (e) |P=0.371 P=0.757 P=0.722 P=0.522 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.348 P=0.760 P=0.765N P=0.517 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.351 P=0.747 P=0.753N P=0.500 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.437 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Cytoplasmic Alteration Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 1/50 (2%) 3/50 (6%) |3/50 (6%) 0/49 (0%) 1/50 (2%) 5/50 (10%) | |POLY-3 RATE (b) | 2/46.41 1/45.93 1/45.22 3/44.80 |3/46.28 0/44.59 1/41.26 5/48.35 | |POLY-3 PERCENT (g) | 4.3% 2.2% 2.2% 6.7% |6.5% 0.0% 2.4% 10.3% | |TERMINAL (d) | 1/35 (3%) 1/40 (3%) 0/36 (0%) 1/35 (3%) |2/40 (5%) 0/39 (0%) 0/28 (0%) 4/42 (10%) | |FIRST INCIDENCE | 651 729 (T) 471 598 |653 --- 580 638 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.262 P=0.472N P=0.507N P=0.480 |P=0.118 P=0.129N P=0.409N P=0.391 | |POLY 3 | P=0.271 P=0.504N P=0.509N P=0.484 |P=0.104 P=0.125N P=0.347N P=0.381 | |POLY 1.5 | P=0.273 P=0.502N P=0.506N P=0.489 |P=0.101 P=0.124N P=0.331N P=0.372 | |POLY 6 | P=0.269 P=0.505N P=0.512N P=0.481 |P=0.107 P=0.126N P=0.369N P=0.393 | |LOGISTIC REGRESSION| P=0.348 P=0.500N P=0.460N P=0.540 |P=0.098 P=0.124N P=0.281N P=0.351 | |COCH-ARM / FISHERS | P=0.280 P=0.500N P=0.500N P=0.500 |P=0.100 P=0.125N P=0.309N P=0.357 | |ORDER RESTRICTED | P=0.277 (e) (e) (e) |P=0.068 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 1/49 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 2/46.41 0/45.93 0/44.49 0/43.91 |0/46.00 1/44.92 0/40.77 0/48.02 | |POLY-3 PERCENT (g) | 4.3% 0.0% 0.0% 0.0% |0.0% 2.2% 0.0% 0.0% | |TERMINAL (d) | 1/35 (3%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 651 --- --- --- |--- 638 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.254N P=0.227N P=0.244N P=0.250N |P=0.511N P=0.500 (e) (e) | |POLY 3 | P=0.240N P=0.240N P=0.247N P=0.250N |P=0.532N P=0.495 (e) (e) | |POLY 1.5 | P=0.241N P=0.238N P=0.243N P=0.245N |P=0.530N P=0.495 (e) (e) | |POLY 6 | P=0.240N P=0.240N P=0.250N P=0.254N |P=0.533N P=0.496 (e) (e) | |LOGISTIC REGRESSION| P=0.238N P=0.239N P=0.233N P=0.233N |P=0.539N P=0.497 (e) (e) | |COCH-ARM / FISHERS | P=0.242N P=0.247N P=0.247N P=0.247N |P=0.525N P=0.495 (e) (e) | |ORDER RESTRICTED | P=0.034N* (e) (e) (e) |P=0.368N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Cortex | | Vacuolization Cytoplasmic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 9/50 (18%) 10/50 (20%) 10/50 (20%) |8/50 (16%) 3/49 (6%) 7/50 (14%) 12/50 (24%) | |POLY-3 RATE (b) | 6/46.13 9/45.93 10/44.49 10/44.22 |8/46.00 3/44.59 7/41.34 12/48.54 | |POLY-3 PERCENT (g) | 13.0% 19.6% 22.5% 22.6% |17.4% 6.7% 16.9% 24.7% | |TERMINAL (d) | 6/35 (17%) 9/40 (23%) 10/36 (28%) 8/35 (23%) |8/40 (20%) 3/39 (8%) 5/28 (18%) 10/42 (24%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 689 |729 (T) 729 (T) 638 644 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.205 P=0.387 P=0.217 P=0.202 |P=0.069 P=0.106N P=0.450 P=0.271 | |POLY 3 | P=0.220 P=0.283 P=0.182 P=0.178 |P=0.063 P=0.108N P=0.589N P=0.268 | |POLY 1.5 | P=0.231 P=0.287 P=0.191 P=0.187 |P=0.058 P=0.107N P=0.555N P=0.251 | |POLY 6 | P=0.213 P=0.283 P=0.176 P=0.173 |P=0.070 P=0.107N P=0.595 P=0.293 | |LOGISTIC REGRESSION| P=0.193 P=0.387 P=0.217 P=0.165 |P=0.070 P=0.106N P=0.560 P=0.270 | |COCH-ARM / FISHERS | P=0.258 P=0.288 P=0.207 P=0.207 |P=0.054 P=0.106N P=0.500N P=0.227 | |ORDER RESTRICTED | P=0.193 (e) (e) (e) |P=0.066 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 5/50 (10%) 3/50 (6%) 7/50 (14%) |1/49 (2%) 1/49 (2%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 7/46.82 5/45.93 3/44.49 7/44.18 |1/45.00 1/44.59 1/40.77 2/48.02 | |POLY-3 PERCENT (g) | 15.0% 10.9% 6.7% 15.9% |2.2% 2.2% 2.5% 4.2% | |TERMINAL (d) | 3/35 (9%) 5/40 (13%) 3/36 (8%) 5/35 (14%) |1/39 (3%) 1/39 (3%) 1/28 (4%) 2/42 (5%) | |FIRST INCIDENCE | 643 729 (T) 729 (T) 687 |729 (T) 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.390 P=0.327N P=0.167N P=0.587 |P=0.368 P=0.762 P=0.686 P=0.526 | |POLY 3 | P=0.402 P=0.393N P=0.179N P=0.568 |P=0.371 P=0.759 P=0.738 P=0.523 | |POLY 1.5 | P=0.413 P=0.386N P=0.170N P=0.584 |P=0.365 P=0.759 P=0.749 P=0.517 | |POLY 6 | P=0.392 P=0.401N P=0.187N P=0.552 |P=0.378 P=0.759 P=0.724 P=0.530 | |LOGISTIC REGRESSION| P=0.391 P=0.381N P=0.169N P=0.582 |P=0.368 P=0.762 P=0.686 P=0.526 | |COCH-ARM / FISHERS | P=0.435 P=0.380N P=0.159N P=0.613N |P=0.355 P=0.753N P=0.747N P=0.508 | |ORDER RESTRICTED | P=0.375 (e) (e) (e) |P=0.447 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia Focal Histiocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/47 (2%) 0/50 (0%) |0/49 (0%) 1/50 (2%) 0/50 (0%) 4/50 (8%) | |POLY-3 RATE (b) | 0/46.13 1/45.93 1/42.59 0/43.91 |0/45.49 1/44.99 0/40.77 4/48.18 | |POLY-3 PERCENT (g) | 0.0% 2.2% 2.4% 0.0% |0.0% 2.2% 0.0% 8.3% | |TERMINAL (d) | 0/35 (0%) 1/40 (3%) 1/35 (3%) 0/35 (0%) |0/40 (0%) 1/39 (3%) 0/28 (0%) 3/42 (7%) | |FIRST INCIDENCE | --- 729 (T) 729 (T) --- |--- 729 (T) --- 689 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.550N P=0.527 P=0.500 (e) |P=0.020 * P=0.495 (e) P=0.074 | |POLY 3 | P=0.548N P=0.499 P=0.484 (e) |P=0.014 * P=0.498 (e) P=0.068 | |POLY 1.5 | P=0.544N P=0.500 P=0.485 (e) |P=0.014 * P=0.500 (e) P=0.066 | |POLY 6 | P=0.551N P=0.499 P=0.484 (e) |P=0.014 * P=0.496 (e) P=0.071 | |LOGISTIC REGRESSION| (e) P=0.527 P=0.500 (e) |P=0.019 * P=0.495 (e) P=0.069 | |COCH-ARM / FISHERS | P=0.536N P=0.500 P=0.485 (e) |P=0.015 * P=0.505 (e) P=0.061 | |ORDER RESTRICTED | P=0.394 (e) (e) (e) |P=0.007 ** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Bone Marrow: Myeloid Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/47 (0%) 5/50 (10%) |2/49 (4%) 3/50 (6%) 5/50 (10%) 2/50 (4%) | |POLY-3 RATE (b) | 0/46.13 1/45.93 0/42.59 5/44.23 |2/45.49 3/45.44 5/41.00 2/48.02 | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 11.3% |4.4% 6.6% 12.2% 4.2% | |TERMINAL (d) | 0/35 (0%) 1/40 (3%) 0/35 (0%) 3/35 (9%) |2/40 (5%) 2/39 (5%) 4/28 (14%) 2/42 (5%) | |FIRST INCIDENCE | --- 729 (T) --- 687 |729 (T) 598 668 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.002 ** P=0.527 (e) P=0.034 * |P=0.559N P=0.487 P=0.105 P=0.677N | |POLY 3 | P=0.002 ** P=0.499 (e) P=0.027 * |P=0.546N P=0.500 P=0.176 P=0.674N | |POLY 1.5 | P=0.002 ** P=0.500 (e) P=0.028 * |P=0.555N P=0.503 P=0.194 P=0.679N | |POLY 6 | P=0.002 ** P=0.499 (e) P=0.026 * |P=0.534N P=0.498 P=0.155 P=0.668N | |LOGISTIC REGRESSION| P=0.002 ** P=0.527 (e) P=0.029 * |P=0.553N P=0.508 P=0.138 P=0.677N | |COCH-ARM / FISHERS | P=0.003 ** P=0.500 (e) P=0.028 * |P=0.570N P=0.510 P=0.226 P=0.684N | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P=0.393 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Bone Marrow: Myeloid Cell, Erythroid Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/47 (0%) 0/50 (0%) |0/49 (0%) 2/50 (4%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/42.59 0/43.91 |0/45.49 2/44.99 1/40.77 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 4.5% 2.5% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/35 (0%) 0/35 (0%) |0/40 (0%) 2/39 (5%) 1/28 (4%) 0/42 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- 729 (T) 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.422N P=0.233 P=0.429 (e) | |POLY 3 | (e) (e) (e) (e) |P=0.415N P=0.235 P=0.478 (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.417N P=0.238 P=0.488 (e) | |POLY 6 | (e) (e) (e) (e) |P=0.412N P=0.232 P=0.465 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) P=0.233 P=0.429 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.420N P=0.253 P=0.505 (e) | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.300N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Brain | | Compression Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 4/50 (8%) 1/50 (2%) |10/50 (20%) 8/49 (16%) 12/50 (24%) 4/50 (8%) | |POLY-3 RATE (b) | 4/46.26 2/45.93 4/46.05 1/43.91 |10/47.20 8/45.91 12/43.24 4/48.36 | |POLY-3 PERCENT (g) | 8.7% 4.4% 8.7% 2.3% |21.2% 17.4% 27.8% 8.3% | |TERMINAL (d) | 3/35 (9%) 2/40 (5%) 1/36 (3%) 1/35 (3%) |6/40 (15%) 5/39 (13%) 5/28 (18%) 2/42 (5%) | |FIRST INCIDENCE | 694 729 (T) 392 729 (T) |602 425 532 644 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.219N P=0.290N P=0.638N P=0.187N |P=0.103N P=0.421N P=0.189 P=0.068N | |POLY 3 | P=0.216N P=0.341N P=0.641 P=0.195N |P=0.080N P=0.422N P=0.315 P=0.066N | |POLY 1.5 | P=0.210N P=0.339N P=0.641 P=0.190N |P=0.085N P=0.418N P=0.348 P=0.068N | |POLY 6 | P=0.222N P=0.341N P=0.642 P=0.200N |P=0.075N P=0.427N P=0.277 P=0.063N | |LOGISTIC REGRESSION| P=0.170N P=0.334N P=0.601N P=0.198N |P=0.100N P=0.405N P=0.426 P=0.085N | |COCH-ARM / FISHERS | P=0.196N P=0.339N P=0.643N P=0.181N |P=0.094N P=0.416N P=0.405 P=0.074N | |ORDER RESTRICTED | P=0.160N (e) (e) (e) |P=0.053N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Brain | | Hemorrhage Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 2/50 (4%) 1/50 (2%) |2/50 (4%) 1/49 (2%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 2/46.89 3/47.22 2/45.29 1/44.36 |2/46.59 1/45.39 2/41.66 0/48.02 | |POLY-3 PERCENT (g) | 4.3% 6.4% 4.4% 2.3% |4.3% 2.2% 4.8% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 603 521 583 598 |583 425 548 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.331N P=0.487 P=0.668 P=0.536N |P=0.209N P=0.513N P=0.621 P=0.232N | |POLY 3 | P=0.323N P=0.503 P=0.681 P=0.519N |P=0.201N P=0.509N P=0.653 P=0.231N | |POLY 1.5 | P=0.316N P=0.503 P=0.686 P=0.513N |P=0.204N P=0.508N P=0.669 P=0.233N | |POLY 6 | P=0.330N P=0.505 P=0.679 P=0.526N |P=0.197N P=0.510N P=0.633 P=0.228N | |LOGISTIC REGRESSION| P=0.181N P=0.462 P=0.656N P=0.430N |P=0.209N P=0.500N P=0.605N P=0.282N | |COCH-ARM / FISHERS | P=0.300N P=0.500 P=0.691N P=0.500N |P=0.207N P=0.508N P=0.691N P=0.247N | |ORDER RESTRICTED | P=0.380N (e) (e) (e) |P=0.150N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Brain | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/49 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 1/46.46 1/46.44 0/44.49 0/43.91 |0/46.00 0/44.59 2/41.66 0/48.02 | |POLY-3 PERCENT (g) | 2.2% 2.2% 0.0% 0.0% |0.0% 0.0% 4.8% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 638 572 --- --- |--- --- 548 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.318N P=0.748 P=0.513N P=0.527N |P=0.584 (e) P=0.212 (e) | |POLY 3 | P=0.307N P=0.760 P=0.509N P=0.511N |P=0.611 (e) P=0.216 (e) | |POLY 1.5 | P=0.306N P=0.760N P=0.505N P=0.507N |P=0.598 (e) P=0.224 (e) | |POLY 6 | P=0.309N P=0.760N P=0.511N P=0.515N |P=0.625 (e) P=0.206 (e) | |LOGISTIC REGRESSION| P=0.239N P=0.729 P=0.483N P=0.472N |P=0.559 (e) P=0.305 (e) | |COCH-ARM / FISHERS | P=0.303N P=0.753N P=0.500N P=0.500N |P=0.576 (e) P=0.247 (e) | |ORDER RESTRICTED | P=0.262N (e) (e) (e) |P=0.228 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Clitoral Gland | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |6/50 (12%) 4/49 (8%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | |6/46.39 4/43.99 1/41.10 1/48.02 | |POLY-3 PERCENT (g) | |12.9% 9.1% 2.4% 2.1% | |TERMINAL (d) | |5/40 (13%) 4/38 (11%) 0/28 (0%) 1/42 (2%) | |FIRST INCIDENCE | |616 729 (T) 638 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.024N* P=0.401N P=0.122N P=0.052N | |POLY 3 | |P=0.019N* P=0.403N P=0.078N P=0.051N | |POLY 1.5 | |P=0.020N* P=0.395N P=0.069N P=0.053N | |POLY 6 | |P=0.019N* P=0.411N P=0.091N P=0.048N* | |LOGISTIC REGRESSION| |P=0.021N* P=0.399N P=0.067N P=0.056N | |COCH-ARM / FISHERS | |P=0.022N* P=0.383N P=0.056N P=0.056N | |ORDER RESTRICTED | |P=0.019N* (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Clitoral Gland | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |1/50 (2%) 4/49 (8%) 3/50 (6%) 1/50 (2%) | |POLY-3 RATE (b) | |1/46.00 4/43.99 3/40.84 1/48.02 | |POLY-3 PERCENT (g) | |2.2% 9.1% 7.3% 2.1% | |TERMINAL (d) | |1/40 (3%) 4/38 (11%) 2/28 (7%) 1/42 (2%) | |FIRST INCIDENCE | |729 (T) 729 (T) 710 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.390N P=0.164 P=0.193 P=0.751N | |POLY 3 | |P=0.377N P=0.165 P=0.264 P=0.751N | |POLY 1.5 | |P=0.386N P=0.168 P=0.280 P=0.755N | |POLY 6 | |P=0.366N P=0.163 P=0.245 P=0.746N | |LOGISTIC REGRESSION| |P=0.371N P=0.164 P=0.217 P=0.751N | |COCH-ARM / FISHERS | |P=0.398N P=0.175 P=0.309 P=0.753N | |ORDER RESTRICTED | |P=0.285N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/50 (4%) 5/49 (10%) 4/50 (8%) 0/50 (0%) | |POLY-3 RATE (b) | |2/46.00 5/43.99 4/41.43 0/48.02 | |POLY-3 PERCENT (g) | |4.4% 11.4% 9.7% 0.0% | |TERMINAL (d) | |2/40 (5%) 5/38 (13%) 1/28 (4%) 0/42 (0%) | |FIRST INCIDENCE | |729 (T) 729 (T) 665 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.121N P=0.195 P=0.223 P=0.228N | |POLY 3 | |P=0.103N P=0.198 P=0.290 P=0.228N | |POLY 1.5 | |P=0.109N P=0.202 P=0.308 P=0.232N | |POLY 6 | |P=0.096N P=0.195 P=0.271 P=0.223N | |LOGISTIC REGRESSION| |P=0.113N P=0.195 P=0.300 (e) | |COCH-ARM / FISHERS | |P=0.119N P=0.210 P=0.339 P=0.247N | |ORDER RESTRICTED | |P=0.059N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Eye | | Cataract | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 0/50 (0%) 1/46 (2%) 0/50 (0%) |1/50 (2%) 2/49 (4%) 2/49 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 1/45.14 0/45.93 1/41.09 0/43.91 |1/46.00 2/44.59 2/40.53 1/48.02 | |POLY-3 PERCENT (g) | 2.2% 0.0% 2.4% 0.0% |2.2% 4.5% 4.9% 2.1% | |TERMINAL (d) | 1/35 (3%) 0/40 (0%) 1/35 (3%) 0/35 (0%) |1/40 (3%) 2/39 (5%) 1/28 (4%) 1/42 (2%) | |FIRST INCIDENCE | 729 (T) --- 729 (T) --- |729 (T) 729 (T) 548 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.476N P=0.473N P=0.762 P=0.500N |P=0.534N P=0.491 P=0.408 P=0.751N | |POLY 3 | P=0.470N P=0.497N P=0.740 P=0.506N |P=0.526N P=0.489 P=0.456 P=0.751N | |POLY 1.5 | P=0.467N P=0.496N P=0.742 P=0.502N |P=0.533N P=0.491 P=0.470 P=0.755N | |POLY 6 | P=0.473N P=0.496N P=0.740 P=0.508N |P=0.518N P=0.489 P=0.439 P=0.746N | |LOGISTIC REGRESSION| P=0.476N (e) P=0.762 (e) |P=0.540N P=0.491 P=0.518 P=0.751N | |COCH-ARM / FISHERS | P=0.461N P=0.495N P=0.737 P=0.495N |P=0.542N P=0.492 P=0.492 P=0.753N | |ORDER RESTRICTED | P=0.256N (e) (e) (e) |P=0.500N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Eye: Retina | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 1/46 (2%) 0/50 (0%) |0/50 (0%) 2/49 (4%) 1/49 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 0/45.14 0/45.93 1/41.09 0/43.91 |0/46.00 2/44.59 1/39.96 1/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.4% 0.0% |0.0% 4.5% 2.5% 2.1% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 1/35 (3%) 0/35 (0%) |0/40 (0%) 2/39 (5%) 1/28 (4%) 1/42 (2%) | |FIRST INCIDENCE | --- --- 729 (T) --- |--- 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.795N (e) P=0.500 (e) |P=0.532 P=0.233 P=0.429 P=0.510 | |POLY 3 | P=0.789N (e) P=0.481 (e) |P=0.546 P=0.230 P=0.472 P=0.509 | |POLY 1.5 | P=0.787N (e) P=0.483 (e) |P=0.539 P=0.231 P=0.481 P=0.505 | |POLY 6 | P=0.791N (e) P=0.481 (e) |P=0.556 P=0.230 P=0.461 P=0.513 | |LOGISTIC REGRESSION| (e) (e) P=0.500 (e) |(e) P=0.233 P=0.429 P=0.510 | |COCH-ARM / FISHERS | P=0.782N (e) P=0.484 (e) |P=0.528 P=0.242 P=0.495 P=0.500 | |ORDER RESTRICTED | P=0.364 (e) (e) (e) |P=0.248 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/49 (0%) 2/50 (4%) |2/50 (4%) 0/49 (0%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 0/46.13 1/46.35 0/43.72 2/45.03 |2/46.86 0/44.59 1/41.67 1/48.35 | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 4.4% |4.3% 0.0% 2.4% 2.1% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 605 --- 491 |602 --- 332 638 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.141 P=0.496 (e) P=0.228 |P=0.509N P=0.252N P=0.535N P=0.476N | |POLY 3 | P=0.148 P=0.501 (e) P=0.232 |P=0.517N P=0.248N P=0.541N P=0.489N | |POLY 1.5 | P=0.149 P=0.501 (e) P=0.233 |P=0.520N P=0.246N P=0.524N P=0.493N | |POLY 6 | P=0.147 P=0.502 (e) P=0.231 |P=0.514N P=0.251N P=0.564N P=0.484N | |LOGISTIC REGRESSION| P=0.241 P=0.454 (e) P=0.304 |P=0.586N P=0.237N P=0.285N P=0.612N | |COCH-ARM / FISHERS | P=0.152 P=0.500 (e) P=0.247 |P=0.524N P=0.253N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.071 (e) (e) (e) |P=0.274N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Hyperplasia Focal Histiocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 1/50 (2%) |1/50 (2%) 2/49 (4%) 1/50 (2%) 4/50 (8%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/43.72 1/43.91 |1/46.00 2/44.59 1/40.77 4/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.3% |2.2% 4.5% 2.5% 8.3% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 1/35 (3%) |1/40 (3%) 2/39 (5%) 1/28 (4%) 4/42 (10%) | |FIRST INCIDENCE | --- --- --- 729 (T) |729 (T) 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.205 (e) (e) P=0.500 |P=0.131 P=0.491 P=0.680 P=0.194 | |POLY 3 | P=0.208 (e) (e) P=0.490 |P=0.124 P=0.489 P=0.733 P=0.192 | |POLY 1.5 | P=0.210 (e) (e) P=0.493 |P=0.121 P=0.491 P=0.744 P=0.187 | |POLY 6 | P=0.206 (e) (e) P=0.487 |P=0.127 P=0.489 P=0.719 P=0.199 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.500 |P=0.131 P=0.491 P=0.680 P=0.194 | |COCH-ARM / FISHERS | P=0.215 (e) (e) P=0.500 |P=0.118 P=0.492 P=0.753N P=0.181 | |ORDER RESTRICTED | P=0.111 (e) (e) (e) |P=0.106 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland | | Inflammation Chronic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 2/49 (4%) 3/50 (6%) |0/50 (0%) 0/49 (0%) 3/50 (6%) 1/50 (2%) | |POLY-3 RATE (b) | 1/46.13 0/45.93 2/43.72 3/43.91 |0/46.00 0/44.59 3/40.96 1/48.02 | |POLY-3 PERCENT (g) | 2.2% 0.0% 4.6% 6.8% |0.0% 0.0% 7.3% 2.1% | |TERMINAL (d) | 1/35 (3%) 0/40 (0%) 2/36 (6%) 3/35 (9%) |0/40 (0%) 0/39 (0%) 2/28 (7%) 1/42 (2%) | |FIRST INCIDENCE | 729 (T) --- 729 (T) 729 (T) |--- --- 680 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.091 P=0.473N P=0.510 P=0.305 |P=0.251 (e) P=0.074 P=0.510 | |POLY 3 | P=0.095 P=0.501N P=0.481 P=0.288 |P=0.259 (e) P=0.099 P=0.509 | |POLY 1.5 | P=0.098 P=0.500N P=0.485 P=0.294 |P=0.248 (e) P=0.107 P=0.505 | |POLY 6 | P=0.092 P=0.501N P=0.480 P=0.283 |P=0.271 (e) P=0.091 P=0.513 | |LOGISTIC REGRESSION| P=0.091 (e) P=0.510 P=0.305 |P=0.248 (e) P=0.092 P=0.510 | |COCH-ARM / FISHERS | P=0.105 P=0.500N P=0.492 P=0.309 |P=0.233 (e) P=0.121 P=0.500 | |ORDER RESTRICTED | P=0.098 (e) (e) (e) |P=0.097 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Harderian Gland: Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 0/49 (0%) 1/50 (2%) |0/50 (0%) 2/49 (4%) 2/50 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 3/46.32 0/45.93 0/43.72 1/43.91 |0/46.00 2/44.59 2/40.77 1/48.02 | |POLY-3 PERCENT (g) | 6.5% 0.0% 0.0% 2.3% |0.0% 4.5% 4.9% 2.1% | |TERMINAL (d) | 1/35 (3%) 0/40 (0%) 0/36 (0%) 1/35 (3%) |0/40 (0%) 2/39 (5%) 2/28 (7%) 1/42 (2%) | |FIRST INCIDENCE | 694 --- --- 729 (T) |--- 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.473N P=0.115N P=0.125N P=0.324N |P=0.496 P=0.233 P=0.164 P=0.510 | |POLY 3 | P=0.452N P=0.120N P=0.129N P=0.325N |P=0.516 P=0.230 P=0.211 P=0.509 | |POLY 1.5 | P=0.451N P=0.119N P=0.127N P=0.318N |P=0.506 P=0.231 P=0.221 P=0.505 | |POLY 6 | P=0.453N P=0.121N P=0.131N P=0.331N |P=0.528 P=0.230 P=0.199 P=0.513 | |LOGISTIC REGRESSION| P=0.465N P=0.121N P=0.129N P=0.325N |(e) P=0.233 P=0.164 P=0.510 | |COCH-ARM / FISHERS | P=0.448N P=0.121N P=0.125N P=0.309N |P=0.491 P=0.242 P=0.247 P=0.500 | |ORDER RESTRICTED | P=0.044N* (e) (e) (e) |P=0.204 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 5/50 (10%) 10/50 (20%) 5/50 (10%) |5/50 (10%) 8/49 (16%) 7/50 (14%) 6/50 (12%) | |POLY-3 RATE (b) | 3/47.05 5/47.56 10/45.29 5/44.84 |5/46.00 8/44.70 7/41.42 6/48.02 | |POLY-3 PERCENT (g) | 6.4% 10.5% 22.1% 11.2% |10.9% 17.9% 16.9% 12.5% | |TERMINAL (d) | 2/35 (6%) 2/40 (5%) 8/36 (22%) 3/35 (9%) |5/40 (13%) 7/39 (18%) 5/28 (18%) 6/42 (14%) | |FIRST INCIDENCE | 315 521 548 562 |729 (T) 702 548 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.400 P=0.392 P=0.042 * P=0.348 |P=0.543N P=0.260 P=0.178 P=0.534 | |POLY 3 | P=0.387 P=0.363 P=0.029 * P=0.330 |P=0.528N P=0.257 P=0.307 P=0.530 | |POLY 1.5 | P=0.402 P=0.359 P=0.030 * P=0.337 |P=0.541N P=0.259 P=0.334 P=0.518 | |POLY 6 | P=0.378 P=0.371 P=0.028 * P=0.328 |P=0.511N P=0.257 P=0.274 P=0.545 | |LOGISTIC REGRESSION| P=0.522 P=0.371 P=0.042 * P=0.427 |P=0.517N P=0.259 P=0.276 P=0.534 | |COCH-ARM / FISHERS | P=0.442 P=0.357 P=0.036 * P=0.357 |P=0.551 P=0.264 P=0.380 P=0.500 | |ORDER RESTRICTED | P=0.102 (e) (e) (e) |P=0.397 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Heart | | Cardiomyopathy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 2/46.12 1/44.75 |0/46.00 0/44.59 0/40.77 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.3% 2.2% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- --- 392 395 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.346 (e) P=0.242 P=0.500 |(e) (e) (e) (e) | |POLY 3 | P=0.337 (e) P=0.237 P=0.494 |(e) (e) (e) (e) | |POLY 1.5 | P=0.341 (e) P=0.238 P=0.496 |(e) (e) (e) (e) | |POLY 6 | P=0.333 (e) P=0.237 P=0.492 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.672 (e) P=0.183 P=0.644 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.350 (e) P=0.247 P=0.500 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.167 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Heart | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 4/49 (8%) 3/50 (6%) 2/50 (4%) | |POLY-3 RATE (b) | 0/46.13 1/46.18 0/44.49 0/43.91 |0/46.00 4/45.63 3/41.01 2/48.02 | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 0.0% |0.0% 8.8% 7.3% 4.2% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 2/39 (5%) 2/28 (7%) 2/42 (5%) | |FIRST INCIDENCE | --- 660 --- --- |--- 483 665 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.588N P=0.500 (e) (e) |P=0.439 P=0.065 P=0.076 P=0.249 | |POLY 3 | P=0.578N P=0.500 (e) (e) |P=0.449 P=0.059 P=0.099 P=0.247 | |POLY 1.5 | P=0.577N P=0.500 (e) (e) |P=0.439 P=0.059 P=0.107 P=0.243 | |POLY 6 | P=0.578N P=0.501 (e) (e) |P=0.463 P=0.060 P=0.091 P=0.252 | |LOGISTIC REGRESSION| P=0.557N P=0.488 (e) (e) |P=0.413 P=0.060 P=0.097 P=0.249 | |COCH-ARM / FISHERS | P=0.576N P=0.500 (e) (e) |P=0.423 P=0.056 P=0.121 P=0.247 | |ORDER RESTRICTED | P=0.390N (e) (e) (e) |P=0.097 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Islets, Pancreatic | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/49 (4%) 1/50 (2%) 1/50 (2%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.13 2/45.35 1/44.49 1/43.91 |0/46.00 0/44.59 0/40.77 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 4.4% 2.3% 2.3% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 2/40 (5%) 1/36 (3%) 1/35 (3%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 729 (T) 729 (T) 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.602 P=0.268 P=0.506 P=0.500 |(e) (e) (e) (e) | |POLY 3 | P=0.601 P=0.233 P=0.493 P=0.490 |(e) (e) (e) (e) | |POLY 1.5 | P=0.608 P=0.233 P=0.495 P=0.493 |(e) (e) (e) (e) | |POLY 6 | P=0.596 P=0.234 P=0.491 P=0.487 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.268 P=0.506 P=0.500 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.621 P=0.242 P=0.500 P=0.500 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.269 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Atrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/49 (0%) 0/49 (0%) 1/50 (2%) |0/50 (0%) 2/48 (4%) 1/47 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 0/45.14 0/45.35 0/43.72 1/44.36 |0/46.00 2/43.78 1/38.77 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.3% |0.0% 4.6% 2.6% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 2/39 (5%) 1/28 (4%) 0/42 (0%) | |FIRST INCIDENCE | --- --- --- 598 |--- 729 (T) 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.209 (e) (e) P=0.487 |P=0.422N P=0.233 P=0.429 (e) | |POLY 3 | P=0.212 (e) (e) P=0.497 |P=0.412N P=0.226 P=0.466 (e) | |POLY 1.5 | P=0.213 (e) (e) P=0.499 |P=0.417N P=0.227 P=0.474 (e) | |POLY 6 | P=0.210 (e) (e) P=0.495 |P=0.406N P=0.227 P=0.456 (e) | |LOGISTIC REGRESSION| P=0.265 (e) (e) P=0.549 |(e) P=0.233 P=0.429 (e) | |COCH-ARM / FISHERS | P=0.217 (e) (e) P=0.505 |P=0.422N P=0.237 P=0.485 (e) | |ORDER RESTRICTED | P=0.116 (e) (e) (e) |P=0.291N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 1/49 (2%) 0/49 (0%) 0/50 (0%) |0/50 (0%) 0/48 (0%) 2/47 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 1/45.66 1/45.49 0/43.72 0/43.91 |0/46.00 0/43.78 2/38.99 0/48.02 | |POLY-3 PERCENT (g) | 2.2% 2.2% 0.0% 0.0% |0.0% 0.0% 5.1% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 572 693 --- --- |--- --- 701 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.317N P=0.756 P=0.517N P=0.513N |P=0.583 (e) P=0.184 (e) | |POLY 3 | P=0.304N P=0.760 P=0.509N P=0.508N |P=0.610 (e) P=0.202 (e) | |POLY 1.5 | P=0.303N P=0.760 P=0.505N P=0.504N |P=0.598 (e) P=0.210 (e) | |POLY 6 | P=0.306N P=0.760 P=0.511N P=0.512N |P=0.624 (e) P=0.193 (e) | |LOGISTIC REGRESSION| P=0.256N P=0.737 P=0.482N P=0.439N |P=0.577 (e) P=0.206 (e) | |COCH-ARM / FISHERS | P=0.299N P=0.753N P=0.500N P=0.495N |P=0.576 (e) P=0.232 (e) | |ORDER RESTRICTED | P=0.258N (e) (e) (e) |P=0.215 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 2/49 (4%) 0/49 (0%) 2/50 (4%) |0/50 (0%) 0/48 (0%) 0/47 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/45.14 2/45.35 0/43.72 2/43.91 |0/46.00 0/43.78 0/38.77 1/48.02 | |POLY-3 PERCENT (g) | 0.0% 4.4% 0.0% 4.6% |0.0% 0.0% 0.0% 2.1% | |TERMINAL (d) | 0/35 (0%) 2/40 (5%) 0/36 (0%) 2/35 (6%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 1/42 (2%) | |FIRST INCIDENCE | --- 729 (T) --- 729 (T) |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.269 P=0.268 (e) P=0.238 |P=0.208 (e) (e) P=0.510 | |POLY 3 | P=0.281 P=0.238 (e) P=0.231 |P=0.204 (e) (e) P=0.509 | |POLY 1.5 | P=0.285 P=0.238 (e) P=0.235 |P=0.202 (e) (e) P=0.505 | |POLY 6 | P=0.278 P=0.239 (e) P=0.228 |P=0.208 (e) (e) P=0.513 | |LOGISTIC REGRESSION| (e) P=0.268 (e) P=0.238 |(e) (e) (e) P=0.510 | |COCH-ARM / FISHERS | P=0.294 P=0.247 (e) P=0.253 |P=0.197 (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.111 (e) (e) (e) |P=0.129 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 43/49 (88%) 43/49 (88%) 41/49 (84%) 46/50 (92%) |38/50 (76%) 40/48 (83%) 38/47 (81%) 40/50 (80%) | |POLY-3 RATE (b) | 43/47.99 43/47.27 41/46.03 46/49.61 |38/47.91 40/45.15 38/45.05 40/48.46 | |POLY-3 PERCENT (g) | 89.6% 91.0% 89.1% 92.7% |79.3% 88.6% 84.4% 82.5% | |TERMINAL (d) | 33/35 (94%) 39/40 (98%) 35/36 (97%) 32/35 (91%) |32/40 (80%) 37/39 (95%) 25/28 (89%) 38/42 (91%) | |FIRST INCIDENCE | 315 507 538 249 |602 483 244 644 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.099 P=0.180N P=0.352N P=0.308 |P=0.526 P=0.318 P=0.023 * P=0.592N | |POLY 3 | P=0.370 P=0.552 P=0.606N P=0.422 |P=0.533 P=0.163 P=0.354 P=0.442 | |POLY 1.5 | P=0.320 P=0.581 P=0.530N P=0.389 |P=0.506 P=0.201 P=0.372 P=0.433 | |POLY 6 | P=0.460 P=0.520 P=0.651 P=0.488 |P=0.550 P=0.126 P=0.314 P=0.442 | |LOGISTIC REGRESSION| P=0.167 P=0.608N P=0.504N P=0.348 |P=0.523 P=0.183 P=0.283 P=0.587 | |COCH-ARM / FISHERS | P=0.274 P=0.620N P=0.387N P=0.357 |P=0.449 P=0.259 P=0.370 P=0.405 | |ORDER RESTRICTED | P=0.447 (e) (e) (e) |P=0.328 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 1/49 (2%) 3/49 (6%) 2/50 (4%) |11/50 (22%) 7/48 (15%) 3/47 (6%) 4/50 (8%) | |POLY-3 RATE (b) | 1/45.47 1/45.77 3/44.59 2/44.97 |11/46.39 7/44.56 3/39.66 4/48.18 | |POLY-3 PERCENT (g) | 2.2% 2.2% 6.7% 4.5% |23.7% 15.7% 7.6% 8.3% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 1/36 (3%) 0/35 (0%) |10/40 (25%) 5/39 (13%) 0/28 (0%) 3/42 (7%) | |FIRST INCIDENCE | 638 605 471 249 |616 598 598 689 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.376 P=0.748 P=0.301 P=0.481 |P=0.028N* P=0.239N P=0.082N P=0.038N* | |POLY 3 | P=0.390 P=0.759N P=0.298 P=0.496 |P=0.021N* P=0.244N P=0.040N* P=0.036N* | |POLY 1.5 | P=0.398 P=0.759N P=0.301 P=0.501 |P=0.022N* P=0.246N P=0.035N* P=0.040N* | |POLY 6 | P=0.381 P=0.758N P=0.298 P=0.491 |P=0.020N* P=0.237N P=0.046N* P=0.033N* | |LOGISTIC REGRESSION| P=0.579 P=0.732 P=0.336 P=0.642 |P=0.023N* P=0.250N P=0.037N* P=0.038N* | |COCH-ARM / FISHERS | P=0.408 P=0.753N P=0.309 P=0.508 |P=0.024N* P=0.247N P=0.027N* P=0.045N* | |ORDER RESTRICTED | P=0.321 (e) (e) (e) |P=0.014N* (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/49 (10%) 3/49 (6%) 2/49 (4%) 3/50 (6%) |8/50 (16%) 4/48 (8%) 5/47 (11%) 0/50 (0%) | |POLY-3 RATE (b) | 5/46.11 3/46.61 2/44.32 3/45.42 |8/48.92 4/45.75 5/40.28 0/48.02 | |POLY-3 PERCENT (g) | 10.8% 6.4% 4.5% 6.6% |16.4% 8.7% 12.4% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 1/36 (3%) 0/35 (0%) |2/40 (5%) 0/39 (0%) 1/28 (4%) 0/42 (0%) | |FIRST INCIDENCE | 638 548 538 249 |328 483 526 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.431N P=0.370N P=0.239N P=0.395N |P=0.009N** P=0.207N P=0.416N P=0.005N** | |POLY 3 | P=0.403N P=0.351N P=0.233N P=0.365N |P=0.007N** P=0.212N P=0.413N P=0.004N** | |POLY 1.5 | P=0.395N P=0.352N P=0.226N P=0.356N |P=0.007N** P=0.208N P=0.378N P=0.004N** | |POLY 6 | P=0.413N P=0.348N P=0.239N P=0.375N |P=0.007N** P=0.214N P=0.453N P=0.004N** | |LOGISTIC REGRESSION| P=0.234N P=0.379N P=0.191N P=0.239N |P=0.005N** P=0.076N P=0.145N P=0.006N** | |COCH-ARM / FISHERS | P=0.384N P=0.357N P=0.218N P=0.346N |P=0.007N** P=0.199N P=0.318N P=0.003N** | |ORDER RESTRICTED | P=0.260N (e) (e) (e) |P=0.002N** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Angiectasis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |2/50 (4%) 1/49 (2%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 1/44.49 0/43.91 |2/46.00 1/44.59 2/40.77 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 0.0% |4.4% 2.2% 4.9% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 1/36 (3%) 0/35 (0%) |2/40 (5%) 1/39 (3%) 2/28 (7%) 0/42 (0%) | |FIRST INCIDENCE | --- --- 729 (T) --- |729 (T) 729 (T) 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.795N (e) P=0.506 (e) |P=0.214N P=0.509N P=0.561 P=0.228N | |POLY 3 | P=0.793N (e) P=0.493 (e) |P=0.196N P=0.511N P=0.650 P=0.228N | |POLY 1.5 | P=0.791N (e) P=0.495 (e) |P=0.201N P=0.509N P=0.667 P=0.232N | |POLY 6 | P=0.795N (e) P=0.491 (e) |P=0.191N P=0.511N P=0.627 P=0.223N | |LOGISTIC REGRESSION| (e) (e) P=0.506 (e) |P=0.214N P=0.509N P=0.561 (e) | |COCH-ARM / FISHERS | P=0.786N (e) P=0.500 (e) |P=0.207N P=0.508N P=0.691N P=0.247N | |ORDER RESTRICTED | P=0.374 (e) (e) (e) |P=0.148N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 23/50 (46%) 23/50 (46%) 8/50 (16%) 2/50 (4%) |42/50 (84%) 44/49 (90%) 43/50 (86%) 39/50 (78%) | |POLY-3 RATE (b) | 23/46.14 23/45.93 8/44.49 2/43.91 |42/47.88 44/48.07 43/47.40 39/48.69 | |POLY-3 PERCENT (g) | 49.9% 50.1% 18.0% 4.6% |87.7% 91.5% 90.7% 80.1% | |TERMINAL (d) | 22/35 (63%) 23/40 (58%) 8/36 (22%) 2/35 (6%) |38/40 (95%) 38/39 (97%) 28/28 (100%) 36/42 (86%) | |FIRST INCIDENCE | 726 729 (T) 729 (T) 729 (T) |328 425 244 638 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001N** P=0.320N P<0.001N** P<0.001N** |P=0.143N P=0.285 P=0.002 ** P=0.142N | |POLY 3 | P<0.001N** P=0.575 P<0.001N** P<0.001N** |P=0.085N P=0.381 P=0.437 P=0.218N | |POLY 1.5 | P<0.001N** P=0.579 P<0.001N** P<0.001N** |P=0.114N P=0.336 P=0.463 P=0.261N | |POLY 6 | P<0.001N** P=0.577 P<0.001N** P<0.001N** |P=0.047N* P=0.454 P=0.409 P=0.156N | |LOGISTIC REGRESSION| (e) P=0.320N P<0.001N** P<0.001N** |P=0.108N P=0.264 P=0.326 P=0.185N | |COCH-ARM / FISHERS | P<0.001N** P=0.579N P<0.001N** P<0.001N** |P=0.145N P=0.290 P=0.500 P=0.306N | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) |P=0.084N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 0/49 (0%) 2/50 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 2/46.06 1/44.36 |0/46.00 0/44.59 2/41.20 1/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.3% 2.3% |0.0% 0.0% 4.9% 2.1% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 1/42 (2%) | |FIRST INCIDENCE | --- --- 392 598 |--- --- 665 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.343 (e) P=0.240 P=0.487 |P=0.257 (e) P=0.197 P=0.510 | |POLY 3 | P=0.333 (e) P=0.237 P=0.492 |P=0.256 (e) P=0.213 P=0.509 | |POLY 1.5 | P=0.338 (e) P=0.237 P=0.495 |P=0.247 (e) P=0.222 P=0.505 | |POLY 6 | P=0.330 (e) P=0.237 P=0.491 |P=0.266 (e) P=0.203 P=0.513 | |LOGISTIC REGRESSION| P=0.574 (e) P=0.203 P=0.547 |P=0.230 (e) P=0.245 P=0.510 | |COCH-ARM / FISHERS | P=0.350 (e) P=0.247 P=0.500 |P=0.234 (e) P=0.247 P=0.500 | |ORDER RESTRICTED | P=0.167 (e) (e) (e) |P=0.149 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Degeneration Cystic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 3/50 (6%) 2/50 (4%) 7/50 (14%) |0/50 (0%) 1/49 (2%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 4/46.80 3/45.93 2/44.81 7/44.06 |0/46.00 1/44.59 0/40.77 2/48.02 | |POLY-3 PERCENT (g) | 8.6% 6.5% 4.5% 15.9% |0.0% 2.2% 0.0% 4.2% | |TERMINAL (d) | 1/35 (3%) 3/40 (8%) 1/36 (3%) 6/35 (17%) |0/40 (0%) 1/39 (3%) 0/28 (0%) 2/42 (5%) | |FIRST INCIDENCE | 638 729 (T) 641 689 |--- 729 (T) --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.084 P=0.462N P=0.352N P=0.249 |P=0.164 P=0.495 (e) P=0.249 | |POLY 3 | P=0.088 P=0.510N P=0.357N P=0.227 |P=0.154 P=0.494 (e) P=0.247 | |POLY 1.5 | P=0.092 P=0.505N P=0.350N P=0.239 |P=0.152 P=0.495 (e) P=0.243 | |POLY 6 | P=0.084 P=0.516N P=0.364N P=0.215 |P=0.157 P=0.494 (e) P=0.252 | |LOGISTIC REGRESSION| P=0.090 P=0.500N P=0.323N P=0.241 |(e) P=0.495 (e) P=0.249 | |COCH-ARM / FISHERS | P=0.102 P=0.500N P=0.339N P=0.262 |P=0.150 P=0.495 (e) P=0.247 | |ORDER RESTRICTED | P=0.087 (e) (e) (e) |P=0.080 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 6/50 (12%) 1/50 (2%) |0/50 (0%) 0/49 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 3/46.31 0/45.93 6/44.49 1/43.91 |0/46.00 0/44.59 1/40.77 0/48.02 | |POLY-3 PERCENT (g) | 6.5% 0.0% 13.5% 2.3% |0.0% 0.0% 2.5% 0.0% | |TERMINAL (d) | 1/35 (3%) 0/40 (0%) 6/36 (17%) 1/35 (3%) |0/40 (0%) 0/39 (0%) 1/28 (4%) 0/42 (0%) | |FIRST INCIDENCE | 696 --- 729 (T) 729 (T) |--- --- 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.449N P=0.112N P=0.254 P=0.320N |P=0.674 (e) P=0.429 (e) | |POLY 3 | P=0.449N P=0.120N P=0.222 P=0.325N |P=0.707 (e) P=0.476 (e) | |POLY 1.5 | P=0.439N P=0.119N P=0.230 P=0.318N |P=0.697 (e) P=0.485 (e) | |POLY 6 | P=0.460N P=0.121N P=0.216 P=0.331N |P=0.718 (e) P=0.464 (e) | |LOGISTIC REGRESSION| P=0.452N P=0.121N P=0.222 P=0.325N |(e) (e) P=0.429 (e) | |COCH-ARM / FISHERS | P=0.418N P=0.121N P=0.243 P=0.309N |P=0.680 (e) P=0.500 (e) | |ORDER RESTRICTED | P=0.258 (e) (e) (e) |P=0.361 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Fatty Change | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 2/49 (4%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 0/43.91 |0/46.00 2/45.15 1/41.38 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 4.4% 2.4% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- 598 532 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.417N P=0.232 P=0.487 (e) | |POLY 3 | (e) (e) (e) (e) |P=0.412N P=0.233 P=0.479 (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.416N P=0.233 P=0.487 (e) | |POLY 6 | (e) (e) (e) (e) |P=0.405N P=0.235 P=0.469 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.442N P=0.235 P=0.611 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.422N P=0.242 P=0.500 (e) | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.301N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 2/44.87 |0/46.00 0/44.59 0/40.77 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.5% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 1/35 (3%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- --- --- 249 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.040 * (e) (e) P=0.240 |(e) (e) (e) (e) | |POLY 3 | P=0.039 * (e) (e) P=0.231 |(e) (e) (e) (e) | |POLY 1.5 | P=0.040 * (e) (e) P=0.234 |(e) (e) (e) (e) | |POLY 6 | P=0.039 * (e) (e) P=0.228 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.096 (e) (e) P=0.325 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.042 * (e) (e) P=0.247 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.027 * (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 0/49 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 0/43.91 |2/46.00 0/44.59 0/40.77 2/48.33 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.4% 0.0% 0.0% 4.1% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |2/40 (5%) 0/39 (0%) 0/28 (0%) 1/42 (2%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) --- --- 644 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.486 P=0.244N P=0.320N P=0.672N | |POLY 3 | (e) (e) (e) (e) |P=0.482 P=0.244N P=0.265N P=0.676N | |POLY 1.5 | (e) (e) (e) (e) |P=0.479 P=0.243N P=0.254N P=0.683N | |POLY 6 | (e) (e) (e) (e) |P=0.486 P=0.244N P=0.280N P=0.666N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.482 (e) (e) P=0.693 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.476 P=0.253N P=0.247N P=0.691N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.267N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 5/50 (10%) 4/50 (8%) 9/50 (18%) |6/50 (12%) 11/49 (22%) 14/50 (28%) 13/50 (26%) | |POLY-3 RATE (b) | 6/46.41 5/46.13 4/44.72 9/45.27 |6/46.39 11/45.23 14/44.95 13/48.02 | |POLY-3 PERCENT (g) | 12.9% 10.8% 8.9% 19.9% |12.9% 24.3% 31.2% 27.1% | |TERMINAL (d) | 4/35 (11%) 4/40 (10%) 3/36 (8%) 6/35 (17%) |5/40 (13%) 9/39 (23%) 6/28 (21%) 13/42 (31%) | |FIRST INCIDENCE | 668 675 668 491 |616 598 332 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.122 P=0.433N P=0.367N P=0.282 |P=0.098 P=0.136 P=0.013 * P=0.079 | |POLY 3 | P=0.134 P=0.504N P=0.393N P=0.269 |P=0.087 P=0.128 P=0.030 * P=0.071 | |POLY 1.5 | P=0.136 P=0.501N P=0.385N P=0.274 |P=0.082 P=0.129 P=0.033 * P=0.067 | |POLY 6 | P=0.132 P=0.505N P=0.399N P=0.266 |P=0.093 P=0.129 P=0.026 * P=0.076 | |LOGISTIC REGRESSION| P=0.135 P=0.503N P=0.392N P=0.288 |P=0.068 P=0.129 P=0.071 P=0.082 | |COCH-ARM / FISHERS | P=0.144 P=0.500N P=0.370N P=0.288 |P=0.074 P=0.133 P=0.039 * P=0.062 | |ORDER RESTRICTED | P=0.157 (e) (e) (e) |P=0.043 * (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Hyperplasia Focal Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 0/49 (0%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 1/46.26 0/45.93 2/44.49 1/44.45 |0/46.00 0/44.59 1/40.88 1/48.02 | |POLY-3 PERCENT (g) | 2.2% 0.0% 4.5% 2.3% |0.0% 0.0% 2.5% 2.1% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 2/36 (6%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 1/42 (2%) | |FIRST INCIDENCE | 694 --- 729 (T) 562 |--- --- 702 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.533 P=0.505N P=0.504 P=0.744 |P=0.243 (e) P=0.444 P=0.510 | |POLY 3 | P=0.535 P=0.501N P=0.486 P=0.752 |P=0.244 (e) P=0.476 P=0.509 | |POLY 1.5 | P=0.539 P=0.501N P=0.492 P=0.754 |P=0.238 (e) P=0.486 P=0.505 | |POLY 6 | P=0.531 P=0.502N P=0.483 P=0.750 |P=0.251 (e) P=0.465 P=0.513 | |LOGISTIC REGRESSION| P=0.571 P=0.501N P=0.486 P=0.731N |P=0.238 (e) P=0.483 P=0.510 | |COCH-ARM / FISHERS | P=0.552 P=0.500N P=0.500 P=0.753N |P=0.227 (e) P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.365 (e) (e) (e) |P=0.229 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 0/43.91 |0/46.00 0/44.59 0/40.77 2/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 4.2% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 2/42 (5%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.054 (e) (e) P=0.249 | |POLY 3 | (e) (e) (e) (e) |P=0.046 * (e) (e) P=0.247 | |POLY 1.5 | (e) (e) (e) (e) |P=0.045 * (e) (e) P=0.243 | |POLY 6 | (e) (e) (e) (e) |P=0.047 * (e) (e) P=0.252 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) P=0.249 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.045 * (e) (e) P=0.247 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.033 * (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 25/50 (50%) 30/50 (60%) 27/50 (54%) 36/50 (72%) |42/50 (84%) 44/49 (90%) 34/50 (68%) 38/50 (76%) | |POLY-3 RATE (b) | 25/47.41 30/46.76 27/46.41 36/46.74 |42/47.88 44/48.26 34/45.77 38/48.85 | |POLY-3 PERCENT (g) | 52.7% 64.2% 58.2% 77.0% |87.7% 91.2% 74.3% 77.8% | |TERMINAL (d) | 22/35 (63%) 28/40 (70%) 23/36 (64%) 29/35 (83%) |37/40 (93%) 37/39 (95%) 24/28 (86%) 34/42 (81%) | |FIRST INCIDENCE | 315 548 392 395 |588 425 244 638 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.008 ** P=0.440 P=0.464 P=0.018 * |P=0.068N P=0.306 P=0.272 P=0.120N | |POLY 3 | P=0.013 * P=0.174 P=0.372 P=0.009 ** |P=0.035N* P=0.408 P=0.065N P=0.146N | |POLY 1.5 | P=0.015 * P=0.187 P=0.388 P=0.011 * |P=0.044N* P=0.367 P=0.052N P=0.172N | |POLY 6 | P=0.012 * P=0.168 P=0.365 P=0.008 ** |P=0.026N* P=0.447 P=0.100N P=0.117N | |LOGISTIC REGRESSION| P=0.012 * P=0.196 P=0.387 P=0.012 * |P=0.042N* P=0.257 P=0.113N P=0.111N | |COCH-ARM / FISHERS | P=0.024 * P=0.211 P=0.421 P=0.020 * |P=0.064N P=0.290 P=0.050N P=0.227N | |ORDER RESTRICTED | P=0.007 ** (e) (e) (e) |P=0.043N* (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 12/50 (24%) 11/50 (22%) 4/50 (8%) 11/50 (22%) |18/50 (36%) 23/49 (47%) 22/50 (44%) 42/50 (84%) | |POLY-3 RATE (b) | 12/46.49 11/45.93 4/44.49 11/45.57 |18/47.62 23/46.15 22/44.73 42/49.01 | |POLY-3 PERCENT (g) | 25.8% 24.0% 9.0% 24.1% |37.8% 49.8% 49.2% 85.7% | |TERMINAL (d) | 10/35 (29%) 11/40 (28%) 4/36 (11%) 8/35 (23%) |14/40 (35%) 19/39 (49%) 11/28 (39%) 36/42 (86%) | |FIRST INCIDENCE | 668 729 (T) 729 (T) 491 |588 483 496 638 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.533 P=0.370N P=0.025N* P=0.515N |P<0.001 ** P=0.194 P=0.059 P<0.001 ** | |POLY 3 | P=0.539N P=0.514N P=0.031N* P=0.522N |P<0.001 ** P=0.165 P=0.184 P<0.001 ** | |POLY 1.5 | P=0.538N P=0.506N P=0.029N* P=0.517N |P<0.001 ** P=0.173 P=0.212 P<0.001 ** | |POLY 6 | P=0.538N P=0.521N P=0.033N* P=0.524N |P<0.001 ** P=0.161 P=0.158 P<0.001 ** | |LOGISTIC REGRESSION| P=0.549 P=0.488N P=0.032N* P=0.517N |P<0.001 ** P=0.180 P=0.251 P<0.001 ** | |COCH-ARM / FISHERS | P=0.528N P=0.500N P=0.027N* P=0.500N |P<0.001 ** P=0.184 P=0.270 P<0.001 ** | |ORDER RESTRICTED | P=0.214N (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 14/50 (28%) 16/50 (32%) 23/50 (46%) 26/50 (52%) |15/50 (30%) 14/49 (29%) 11/50 (22%) 26/50 (52%) | |POLY-3 RATE (b) | 14/46.26 16/46.13 23/44.49 26/44.56 |15/47.48 14/44.78 11/41.22 26/48.35 | |POLY-3 PERCENT (g) | 30.3% 34.7% 51.7% 58.4% |31.6% 31.3% 26.7% 53.8% | |TERMINAL (d) | 13/35 (37%) 15/40 (38%) 23/36 (64%) 23/35 (66%) |12/40 (30%) 13/39 (33%) 10/28 (36%) 25/42 (60%) | |FIRST INCIDENCE | 696 675 729 (T) 618 |328 680 598 638 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.002 ** P=0.577 P=0.043 * P=0.009 ** |P=0.012 * P=0.531N P=0.573 P=0.035 * | |POLY 3 | P=0.002 ** P=0.408 P=0.028 * P=0.005 ** |P=0.007 ** P=0.575N P=0.393N P=0.021 * | |POLY 1.5 | P=0.003 ** P=0.412 P=0.034 * P=0.006 ** |P=0.007 ** P=0.559N P=0.335N P=0.020 * | |POLY 6 | P=0.002 ** P=0.409 P=0.022 * P=0.004 ** |P=0.008 ** P=0.585N P=0.467N P=0.023 * | |LOGISTIC REGRESSION| P<0.001 ** P=0.437 P=0.029 * P=0.004 ** |P=0.014 * P=0.532N P=0.327N P=0.023 * | |COCH-ARM / FISHERS | P=0.007 ** P=0.414 P=0.048 * P=0.012 * |P=0.009 ** P=0.526N P=0.247N P=0.021 * | |ORDER RESTRICTED | P=0.003 ** (e) (e) (e) |P=0.006 ** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 1/49 (2%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 2/46.64 0/45.93 2/44.59 1/44.36 |0/46.00 1/44.78 0/40.77 1/48.33 | |POLY-3 PERCENT (g) | 4.3% 0.0% 4.5% 2.3% |0.0% 2.2% 0.0% 2.1% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 1/36 (3%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 638 --- 703 598 |--- 680 --- 644 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.617N P=0.252N P=0.682 P=0.529N |P=0.446 P=0.505 (e) P=0.517 | |POLY 3 | P=0.608N P=0.241N P=0.678 P=0.518N |P=0.438 P=0.495 (e) P=0.510 | |POLY 1.5 | P=0.605N P=0.239N P=0.684 P=0.512N |P=0.433 P=0.495 (e) P=0.506 | |POLY 6 | P=0.611N P=0.243N P=0.672 P=0.523N |P=0.444 P=0.495 (e) P=0.515 | |LOGISTIC REGRESSION| P=0.564N P=0.247N P=0.688N P=0.451N |P=0.414 P=0.498 (e) P=0.453 | |COCH-ARM / FISHERS | P=0.596N P=0.247N P=0.691N P=0.500N |P=0.427 P=0.495 (e) P=0.500 | |ORDER RESTRICTED | P=0.434N (e) (e) (e) |P=0.261 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 24 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver | | Pigmentation Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 2/44.49 0/43.91 |0/46.00 0/44.59 0/40.77 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.5% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 2/36 (6%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- --- 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.711N (e) P=0.244 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.714N (e) P=0.229 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.709N (e) P=0.232 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.718N (e) P=0.227 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) P=0.244 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.697N (e) P=0.247 (e) |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.241 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver: Bile Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |2/50 (4%) 0/49 (0%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 1/43.91 |2/46.00 0/44.59 1/40.77 1/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.3% |4.4% 0.0% 2.5% 2.1% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 1/35 (3%) |2/40 (5%) 0/39 (0%) 1/28 (4%) 1/42 (2%) | |FIRST INCIDENCE | --- --- --- 729 (T) |729 (T) --- 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.205 (e) (e) P=0.500 |P=0.519N P=0.244N P=0.624N P=0.483N | |POLY 3 | P=0.207 (e) (e) P=0.490 |P=0.519N P=0.244N P=0.542N P=0.485N | |POLY 1.5 | P=0.209 (e) (e) P=0.493 |P=0.522N P=0.243N P=0.525N P=0.491N | |POLY 6 | P=0.205 (e) (e) P=0.487 |P=0.516N P=0.244N P=0.563N P=0.478N | |LOGISTIC REGRESSION| (e) (e) (e) P=0.500 |P=0.519N (e) P=0.624N P=0.483N | |COCH-ARM / FISHERS | P=0.214 (e) (e) P=0.500 |P=0.524N P=0.253N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.111 (e) (e) (e) |P=0.271N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 25 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 49/50 (98%) 49/50 (98%) 47/50 (94%) 49/50 (98%) |20/50 (40%) 29/49 (59%) 20/50 (40%) 40/50 (80%) | |POLY-3 RATE (b) | 49/49.08 49/49.48 47/49.22 49/49.04 |20/46.83 29/46.36 20/41.85 40/49.64 | |POLY-3 PERCENT (g) | 99.8% 99.0% 95.5% 99.9% |42.7% 62.6% 47.8% 80.6% | |TERMINAL (d) | 35/35 (100%) 40/40 (100%) 34/36 (94%) 35/35 (100%)|18/40 (45%) 25/39 (64%) 15/28 (54%) 34/42 (81%) | |FIRST INCIDENCE | 572 507 392 395 |602 425 638 434 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.298 P=0.208N P=0.393N P=0.508 |P<0.001 ** P=0.046 * P=0.129 P<0.001 ** | |POLY 3 | P=0.603 P=0.888N P=0.212N P=1.000 |P<0.001 ** P=0.040 * P=0.394 P<0.001 ** | |POLY 1.5 | P=0.575 P=0.784N P=0.216N P=0.995 |P<0.001 ** P=0.041 * P=0.466 P<0.001 ** | |POLY 6 | P=0.656 P=0.999N P=0.229N P=1.000 |P<0.001 ** P=0.041 * P=0.313 P<0.001 ** | |LOGISTIC REGRESSION| P=0.343 P=0.787N P=0.374N (e) |P<0.001 ** P=0.038 * P=0.300 P<0.001 ** | |COCH-ARM / FISHERS | P=0.618 P=0.753N P=0.309N P=0.753N |P<0.001 ** P=0.044 * P=0.581N P<0.001 ** | |ORDER RESTRICTED | P=0.256N (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver: Hepatocyte | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 3/50 (6%) 2/50 (4%) |0/50 (0%) 0/49 (0%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 1/46.18 1/46.35 3/45.30 2/44.60 |0/46.00 0/44.59 1/40.88 2/48.02 | |POLY-3 PERCENT (g) | 2.2% 2.2% 6.6% 4.5% |0.0% 0.0% 2.5% 4.2% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 1/36 (3%) 1/35 (3%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 2/42 (5%) | |FIRST INCIDENCE | 716 605 583 491 |--- --- 702 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.372 P=0.757N P=0.299 P=0.488 |P=0.079 (e) P=0.444 P=0.249 | |POLY 3 | P=0.380 P=0.760N P=0.298 P=0.488 |P=0.073 (e) P=0.476 P=0.247 | |POLY 1.5 | P=0.386 P=0.760N P=0.301 P=0.492 |P=0.070 (e) P=0.486 P=0.243 | |POLY 6 | P=0.374 P=0.759N P=0.299 P=0.485 |P=0.075 (e) P=0.465 P=0.252 | |LOGISTIC REGRESSION| P=0.479 P=0.753 P=0.324 P=0.544 |P=0.078 (e) P=0.483 P=0.249 | |COCH-ARM / FISHERS | P=0.399 P=0.753N P=0.309 P=0.500 |P=0.067 (e) P=0.500 P=0.247 | |ORDER RESTRICTED | P=0.319 (e) (e) (e) |P=0.080 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 26 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver: Hepatocyte | | Vacuolization Cytoplasmic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 23/50 (46%) 30/50 (60%) 26/50 (52%) 23/50 (46%) |9/50 (18%) 10/49 (20%) 11/50 (22%) 9/50 (18%) | |POLY-3 RATE (b) | 23/46.13 30/45.93 26/44.49 23/44.06 |9/46.10 10/45.30 11/41.45 9/48.02 | |POLY-3 PERCENT (g) | 49.9% 65.3% 58.4% 52.2% |19.5% 22.1% 26.5% 18.7% | |TERMINAL (d) | 23/35 (66%) 30/40 (75%) 26/36 (72%) 22/35 (63%) |8/40 (20%) 9/39 (23%) 10/28 (36%) 9/42 (21%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 689 |703 483 496 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.386N P=0.267 P=0.369 P=0.593 |P=0.509N P=0.476 P=0.130 P=0.557N | |POLY 3 | P=0.370N P=0.091 P=0.267 P=0.496 |P=0.489N P=0.483 P=0.300 P=0.565N | |POLY 1.5 | P=0.343N P=0.102 P=0.296 P=0.524 |P=0.504N P=0.482 P=0.339 P=0.580N | |POLY 6 | P=0.391N P=0.082 P=0.244 P=0.475 |P=0.471N P=0.486 P=0.251 P=0.548N | |LOGISTIC REGRESSION| P=0.452N P=0.267 P=0.369 P=0.481 |P=0.483N P=0.471 P=0.238 P=0.523N | |COCH-ARM / FISHERS | P=0.287N P=0.115 P=0.345 P=0.579N |P=0.525N P=0.480 P=0.402 P=0.602N | |ORDER RESTRICTED | P=0.301 (e) (e) (e) |P=0.507N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver: Hepatocyte, Centrilobular | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/49 (0%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 0/46.13 2/46.86 2/45.48 0/43.91 |0/46.00 0/44.59 1/41.45 1/48.18 | |POLY-3 PERCENT (g) | 0.0% 4.3% 4.4% 0.0% |0.0% 0.0% 2.4% 2.1% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 572 439 --- |--- --- 496 689 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.398N P=0.230 P=0.235 (e) |P=0.242 (e) P=0.496 P=0.523 | |POLY 3 | P=0.401N P=0.241 P=0.234 (e) |P=0.245 (e) P=0.479 P=0.509 | |POLY 1.5 | P=0.394N P=0.240 P=0.235 (e) |P=0.238 (e) P=0.487 P=0.506 | |POLY 6 | P=0.407N P=0.243 P=0.234 (e) |P=0.253 (e) P=0.469 P=0.514 | |LOGISTIC REGRESSION| P=0.246N P=0.171 P=0.255 (e) |P=0.182 (e) P=0.636 P=0.485 | |COCH-ARM / FISHERS | P=0.381N P=0.247 P=0.247 (e) |P=0.227 (e) P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.274 (e) (e) (e) |P=0.233 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 27 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver: Hepatocyte, Centrilobular | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 4/50 (8%) 0/50 (0%) 3/50 (6%) |1/50 (2%) 0/49 (0%) 4/50 (8%) 1/50 (2%) | |POLY-3 RATE (b) | 5/46.76 4/47.41 0/44.49 3/44.01 |1/46.39 0/44.59 4/41.86 1/48.23 | |POLY-3 PERCENT (g) | 10.7% 8.4% 0.0% 6.8% |2.2% 0.0% 9.6% 2.1% | |TERMINAL (d) | 1/35 (3%) 0/40 (0%) 0/36 (0%) 2/35 (6%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 643 548 --- 702 |616 --- 548 675 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.370N P=0.498N P=0.039N* P=0.384N |P=0.444 P=0.504N P=0.133 P=0.736N | |POLY 3 | P=0.353N P=0.491N P=0.035N* P=0.390N |P=0.451 P=0.508N P=0.149 P=0.752N | |POLY 1.5 | P=0.345N P=0.494N P=0.033N* P=0.378N |P=0.437 P=0.506N P=0.160 P=0.755N | |POLY 6 | P=0.362N P=0.486N P=0.037N* P=0.403N |P=0.468 P=0.509N P=0.137 P=0.747N | |LOGISTIC REGRESSION| P=0.299N P=0.514N P=0.032N* P=0.368N |P=0.386 P=0.506N P=0.226 P=0.720 | |COCH-ARM / FISHERS | P=0.333N P=0.500N P=0.028N* P=0.357N |P=0.416 P=0.505N P=0.181 P=0.753N | |ORDER RESTRICTED | P=0.123N (e) (e) (e) |P=0.165 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver: Hepatocyte, Midzonal | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/46.13 1/45.93 2/44.59 0/43.91 |0/46.00 0/44.59 0/40.77 0/48.02 | |POLY-3 PERCENT (g) | 2.2% 2.2% 4.5% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/35 (3%) 1/40 (3%) 1/36 (3%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 703 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.350N P=0.732N P=0.507 P=0.500N |(e) (e) (e) (e) | |POLY 3 | P=0.350N P=0.760 P=0.488 P=0.510N |(e) (e) (e) (e) | |POLY 1.5 | P=0.345N P=0.760 P=0.492 P=0.507N |(e) (e) (e) (e) | |POLY 6 | P=0.354N P=0.760 P=0.486 P=0.513N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.351N P=0.732N P=0.485 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.333N P=0.753N P=0.500 P=0.500N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.277N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 28 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Liver: Serosa | | Fibrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.13 2/45.93 0/44.49 0/43.91 |0/46.00 0/44.59 0/40.77 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 4.4% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 2/40 (5%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 729 (T) --- --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.380N P=0.268 (e) (e) |(e) (e) (e) (e) | |POLY 3 | P=0.375N P=0.236 (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.373N P=0.237 (e) (e) |(e) (e) (e) (e) | |POLY 6 | P=0.377N P=0.236 (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.268 (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.369N P=0.247 (e) (e) |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.256N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Congestion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |2/50 (4%) 4/49 (8%) 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 1/47.05 0/45.93 1/45.33 1/44.75 |2/46.00 4/45.58 2/41.34 2/48.02 | |POLY-3 PERCENT (g) | 2.1% 0.0% 2.2% 2.2% |4.4% 8.8% 4.8% 4.2% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |2/40 (5%) 2/39 (5%) 1/28 (4%) 2/42 (5%) | |FIRST INCIDENCE | 315 --- 392 395 |729 (T) 425 548 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.541 P=0.500N P=0.758N P=0.758 |P=0.422N P=0.335 P=0.587 P=0.677N | |POLY 3 | P=0.532 P=0.505N P=0.752 P=0.749 |P=0.416N P=0.333 P=0.655 P=0.678N | |POLY 1.5 | P=0.536 P=0.503N P=0.755 P=0.753 |P=0.422N P=0.331 P=0.670 P=0.684N | |POLY 6 | P=0.529 P=0.505N P=0.751 P=0.747 |P=0.409N P=0.337 P=0.635 P=0.670N | |LOGISTIC REGRESSION| P=0.537N (e) (e) P=0.665N |P=0.442N P=0.334 P=0.696N P=0.677N | |COCH-ARM / FISHERS | P=0.545 P=0.500N P=0.753N P=0.753N |P=0.428N P=0.329 P=0.691N P=0.691N | |ORDER RESTRICTED | P=0.522 (e) (e) (e) |P=0.479N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 29 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Hemorrhage Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |1/50 (2%) 0/49 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 1/46.26 0/45.93 1/44.98 1/44.00 |1/46.00 0/44.59 0/40.77 2/48.02 | |POLY-3 PERCENT (g) | 2.2% 0.0% 2.2% 2.3% |2.2% 0.0% 0.0% 4.2% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |1/40 (3%) 0/39 (0%) 0/28 (0%) 2/42 (5%) | |FIRST INCIDENCE | 694 --- 583 706 |729 (T) --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.525 P=0.505N P=0.750 P=0.743 |P=0.247 P=0.505N P=0.571N P=0.517 | |POLY 3 | P=0.529 P=0.501N P=0.754 P=0.749 |P=0.238 P=0.506N P=0.524N P=0.515 | |POLY 1.5 | P=0.533 P=0.501N P=0.756 P=0.753 |P=0.236 P=0.505N P=0.515N P=0.509 | |POLY 6 | P=0.524 P=0.502N P=0.753 P=0.746 |P=0.240 P=0.506N P=0.536N P=0.522 | |LOGISTIC REGRESSION| P=0.578 P=0.501N P=0.745N P=0.761 |P=0.247 (e) (e) P=0.517 | |COCH-ARM / FISHERS | P=0.545 P=0.500N P=0.753N P=0.753N |P=0.234 P=0.505N P=0.500N P=0.500 | |ORDER RESTRICTED | P=0.520 (e) (e) (e) |P=0.146 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 2/50 (4%) 2/50 (4%) |6/50 (12%) 6/49 (12%) 7/50 (14%) 1/50 (2%) | |POLY-3 RATE (b) | 3/47.26 3/47.18 2/45.41 2/44.78 |6/48.79 6/48.07 7/44.12 1/48.35 | |POLY-3 PERCENT (g) | 6.4% 6.4% 4.4% 4.5% |12.3% 12.5% 15.9% 2.1% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 572 548 538 598 |328 425 526 638 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.443N P=0.644 P=0.527N P=0.540N |P=0.059N P=0.598 P=0.411 P=0.056N | |POLY 3 | P=0.431N P=0.661 P=0.518N P=0.524N |P=0.057N P=0.610 P=0.423 P=0.058N | |POLY 1.5 | P=0.423N P=0.662N P=0.511N P=0.516N |P=0.056N P=0.608 P=0.450 P=0.058N | |POLY 6 | P=0.438N P=0.662 P=0.524N P=0.532N |P=0.057N P=0.611 P=0.393 P=0.058N | |LOGISTIC REGRESSION| P=0.254N P=0.660 P=0.429N P=0.407N |P=0.045N* P=0.661N P=0.380N P=0.112N | |COCH-ARM / FISHERS | P=0.407N P=0.661N P=0.500N P=0.500N |P=0.054N P=0.606 P=0.500 P=0.056N | |ORDER RESTRICTED | P=0.539N (e) (e) (e) |P=0.044N* (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 30 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Hyperplasia Focal Histiocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/49 (0%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 4/46.39 1/45.93 0/44.49 0/43.91 |0/46.00 0/44.59 1/40.88 1/48.15 | |POLY-3 PERCENT (g) | 8.6% 2.2% 0.0% 0.0% |0.0% 0.0% 2.5% 2.1% | |TERMINAL (d) | 2/35 (6%) 1/40 (3%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 694 729 (T) --- --- |--- --- 702 696 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.063N P=0.160N P=0.065N P=0.071N |P=0.247 (e) P=0.444 P=0.519 | |POLY 3 | P=0.056N P=0.182N P=0.066N P=0.068N |P=0.245 (e) P=0.476 P=0.509 | |POLY 1.5 | P=0.056N P=0.180N P=0.064N P=0.065N |P=0.238 (e) P=0.486 P=0.505 | |POLY 6 | P=0.057N P=0.183N P=0.067N P=0.070N |P=0.253 (e) P=0.465 P=0.514 | |LOGISTIC REGRESSION| P=0.061N P=0.180N P=0.066N P=0.068N |P=0.228 (e) P=0.483 P=0.489 | |COCH-ARM / FISHERS | P=0.057N P=0.181N P=0.059N P=0.059N |P=0.227 (e) P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.007N** (e) (e) (e) |P=0.229 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |0/50 (0%) 3/49 (6%) 1/50 (2%) 6/50 (12%) | |POLY-3 RATE (b) | 2/47.06 1/46.35 1/44.70 0/43.91 |0/46.00 3/44.59 1/41.01 6/48.49 | |POLY-3 PERCENT (g) | 4.3% 2.2% 2.2% 0.0% |0.0% 6.7% 2.4% 12.4% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 3/39 (8%) 0/28 (0%) 4/42 (10%) | |FIRST INCIDENCE | 315 608 673 --- |--- 729 (T) 665 644 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.207N P=0.493N P=0.505N P=0.245N |P=0.020 * P=0.117 P=0.464 P=0.024 * | |POLY 3 | P=0.205N P=0.505N P=0.518N P=0.253N |P=0.013 * P=0.113 P=0.477 P=0.018 * | |POLY 1.5 | P=0.202N P=0.504N P=0.512N P=0.248N |P=0.013 * P=0.114 P=0.486 P=0.017 * | |POLY 6 | P=0.208N P=0.504N P=0.520N P=0.257N |P=0.014 * P=0.113 P=0.466 P=0.020 * | |LOGISTIC REGRESSION| P=0.109N P=0.590N P=0.442N P=0.139N |P=0.015 * P=0.117 P=0.517 P=0.017 * | |COCH-ARM / FISHERS | P=0.194N P=0.500N P=0.500N P=0.247N |P=0.013 * P=0.117 P=0.500 P=0.013 * | |ORDER RESTRICTED | P=0.131N (e) (e) (e) |P=0.004 ** (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 31 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Inflammation Chronic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 2/49 (4%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 0/43.91 |1/46.00 2/44.92 1/40.77 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.2% 4.5% 2.5% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |1/40 (3%) 1/39 (3%) 1/28 (4%) 0/42 (0%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 638 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.232N P=0.494 P=0.680 P=0.490N | |POLY 3 | (e) (e) (e) (e) |P=0.224N P=0.492 P=0.733 P=0.491N | |POLY 1.5 | (e) (e) (e) (e) |P=0.226N P=0.492 P=0.744 P=0.495N | |POLY 6 | (e) (e) (e) (e) |P=0.220N P=0.494 P=0.719 P=0.487N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.227N P=0.494 P=0.680 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.229N P=0.492 P=0.753N P=0.500N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.211N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Metaplasia Focal Osseous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 1/50 (2%) 2/50 (4%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.13 2/45.93 1/44.49 2/43.91 |0/46.00 0/44.59 0/40.77 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 4.4% 2.3% 4.6% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 2/40 (5%) 1/36 (3%) 2/35 (6%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 729 (T) 729 (T) 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.296 P=0.268 P=0.506 P=0.238 |(e) (e) (e) (e) | |POLY 3 | P=0.300 P=0.236 P=0.493 P=0.226 |(e) (e) (e) (e) | |POLY 1.5 | P=0.306 P=0.237 P=0.495 P=0.230 |(e) (e) (e) (e) | |POLY 6 | P=0.295 P=0.236 P=0.491 P=0.223 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.268 P=0.506 P=0.238 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.318 P=0.247 P=0.500 P=0.247 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.147 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 32 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lung | | Metaplasia Osseous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 2/43.91 |0/46.00 0/44.59 0/40.77 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.6% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 2/35 (6%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- --- --- 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.037 * (e) (e) P=0.238 |(e) (e) (e) (e) | |POLY 3 | P=0.038 * (e) (e) P=0.226 |(e) (e) (e) (e) | |POLY 1.5 | P=0.039 * (e) (e) P=0.230 |(e) (e) (e) (e) | |POLY 6 | P=0.038 * (e) (e) P=0.223 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.238 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.042 * (e) (e) P=0.247 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.026 * (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 9/50 (18%) 6/50 (12%) 5/50 (10%) |7/50 (14%) 5/49 (10%) 3/50 (6%) 3/50 (6%) | |POLY-3 RATE (b) | 2/46.13 9/45.93 6/44.62 5/43.91 |7/46.10 5/45.33 3/40.77 3/48.15 | |POLY-3 PERCENT (g) | 4.3% 19.6% 13.5% 11.4% |15.2% 11.0% 7.4% 6.2% | |TERMINAL (d) | 2/35 (6%) 9/40 (23%) 5/36 (14%) 5/35 (14%) |6/40 (15%) 2/39 (5%) 3/28 (11%) 2/42 (5%) | |FIRST INCIDENCE | 729 (T) 729 (T) 696 729 (T) |703 598 729 (T) 696 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.528 P=0.044 * P=0.143 P=0.214 |P=0.110N P=0.400N P=0.337N P=0.141N | |POLY 3 | P=0.530 P=0.024 * P=0.122 P=0.196 |P=0.098N P=0.391N P=0.211N P=0.141N | |POLY 1.5 | P=0.544 P=0.025 * P=0.126 P=0.203 |P=0.101N P=0.393N P=0.189N P=0.148N | |POLY 6 | P=0.518 P=0.024 * P=0.120 P=0.191 |P=0.094N P=0.383N P=0.242N P=0.132N | |LOGISTIC REGRESSION| P=0.516 P=0.044 * P=0.121 P=0.214 |P=0.098N P=0.397N P=0.289N P=0.132N | |COCH-ARM / FISHERS | P=0.573 P=0.026 * P=0.134 P=0.218 |P=0.104N P=0.394N P=0.159N P=0.159N | |ORDER RESTRICTED | P=0.094 (e) (e) (e) |P=0.105N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 33 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 2/50 (4%) 0/50 (0%) 2/50 (4%) |1/49 (2%) 0/49 (0%) 0/49 (0%) 5/50 (10%) | |POLY-3 RATE (b) | 0/43.13 2/45.93 0/44.49 2/43.91 |1/45.49 0/44.59 0/39.96 5/48.05 | |POLY-3 PERCENT (g) | 0.0% 4.4% 0.0% 4.6% |2.2% 0.0% 0.0% 10.4% | |TERMINAL (d) | 0/32 (0%) 2/40 (5%) 0/36 (0%) 2/35 (6%) |1/40 (3%) 0/39 (0%) 0/28 (0%) 4/42 (10%) | |FIRST INCIDENCE | --- 729 (T) --- 729 (T) |729 (T) --- --- 722 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.282 P=0.289 (e) P=0.258 |P=0.012 * P=0.505N P=0.571N P=0.119 | |POLY 3 | P=0.285 P=0.251 (e) P=0.241 |P=0.007 ** P=0.504N P=0.526N P=0.115 | |POLY 1.5 | P=0.289 P=0.252 (e) P=0.244 |P=0.007 ** P=0.502N P=0.516N P=0.112 | |POLY 6 | P=0.283 P=0.252 (e) P=0.239 |P=0.008 ** P=0.505N P=0.538N P=0.119 | |LOGISTIC REGRESSION| (e) P=0.289 (e) P=0.258 |P=0.012 * (e) (e) P=0.123 | |COCH-ARM / FISHERS | P=0.297 P=0.263 (e) P=0.263 |P=0.008 ** P=0.500N P=0.500N P=0.107 | |ORDER RESTRICTED | P=0.119 (e) (e) (e) |P=0.004 ** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |1/49 (2%) 0/49 (0%) 2/49 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 0/43.13 0/45.93 1/44.98 1/44.06 |1/46.39 0/44.59 2/41.03 2/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 2.3% |2.2% 0.0% 4.9% 4.2% | |TERMINAL (d) | 0/32 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 2/42 (5%) | |FIRST INCIDENCE | --- --- 583 689 |328 --- 244 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.295 (e) P=0.487 P=0.490 |P=0.240 P=0.500N P=0.466 P=0.511 | |POLY 3 | P=0.297 (e) P=0.508 P=0.504 |P=0.245 P=0.508N P=0.457 P=0.512 | |POLY 1.5 | P=0.301 (e) P=0.510 P=0.507 |P=0.240 P=0.505N P=0.474 P=0.509 | |POLY 6 | P=0.295 (e) P=0.509 P=0.503 |P=0.252 P=0.509N P=0.437 P=0.517 | |LOGISTIC REGRESSION| P=0.352 (e) P=0.527 P=0.515 |P=0.149 (e) P=0.742N P=0.385 | |COCH-ARM / FISHERS | P=0.310 (e) P=0.515 P=0.515 |P=0.232 P=0.500N P=0.500 P=0.508 | |ORDER RESTRICTED | P=0.255 (e) (e) (e) |P=0.242 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 34 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/47 (2%) 2/50 (4%) 1/50 (2%) 4/50 (8%) |2/49 (4%) 1/49 (2%) 2/49 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 1/43.14 2/46.18 1/44.49 4/45.56 |2/45.49 1/45.30 2/40.91 2/48.02 | |POLY-3 PERCENT (g) | 2.3% 4.3% 2.3% 8.8% |4.4% 2.2% 4.9% 4.2% | |TERMINAL (d) | 0/32 (0%) 1/40 (3%) 1/36 (3%) 2/35 (6%) |2/40 (5%) 0/39 (0%) 0/28 (0%) 2/42 (5%) | |FIRST INCIDENCE | 726 660 729 (T) 249 |729 (T) 483 526 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.104 P=0.538 P=0.747N P=0.193 |P=0.521 P=0.506N P=0.613 P=0.677N | |POLY 3 | P=0.115 P=0.524 P=0.754N P=0.195 |P=0.533 P=0.501N P=0.655 P=0.674N | |POLY 1.5 | P=0.116 P=0.523 P=0.751N P=0.197 |P=0.527 P=0.501N P=0.670 P=0.679N | |POLY 6 | P=0.113 P=0.527 P=0.755N P=0.194 |P=0.540 P=0.501N P=0.637 P=0.668N | |LOGISTIC REGRESSION| P=0.169 P=0.522 P=0.750N P=0.265 |P=0.496 P=0.488N P=0.651N P=0.677N | |COCH-ARM / FISHERS | P=0.116 P=0.523 P=0.737N P=0.201 |P=0.518 P=0.500N P=0.691N P=0.684N | |ORDER RESTRICTED | P=0.108 (e) (e) (e) |P=0.595 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/47 (4%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/49 (0%) 1/49 (2%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 2/43.13 1/45.93 0/44.49 0/43.91 |0/45.49 1/45.30 0/39.96 0/48.02 | |POLY-3 PERCENT (g) | 4.6% 2.2% 0.0% 0.0% |0.0% 2.2% 0.0% 0.0% | |TERMINAL (d) | 2/32 (6%) 1/40 (3%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) --- --- |--- 483 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.168N P=0.422N P=0.213N P=0.219N |P=0.527N P=0.500 (e) (e) | |POLY 3 | P=0.166N P=0.478N P=0.230N P=0.233N |P=0.531N P=0.499 (e) (e) | |POLY 1.5 | P=0.165N P=0.478N P=0.228N P=0.230N |P=0.528N P=0.500 (e) (e) | |POLY 6 | P=0.167N P=0.477N P=0.231N P=0.235N |P=0.533N P=0.499 (e) (e) | |LOGISTIC REGRESSION| P=0.168N P=0.422N (e) (e) |P=0.560N P=0.451 (e) (e) | |COCH-ARM / FISHERS | P=0.163N P=0.477N P=0.232N P=0.232N |P=0.523N P=0.500 (e) (e) | |ORDER RESTRICTED | P=0.072N (e) (e) (e) |P=0.370N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 35 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/49 (4%) 0/49 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/43.13 0/45.93 0/44.49 0/43.91 |2/46.39 0/44.59 0/39.96 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/32 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |1/40 (3%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- --- --- --- |328 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.135N P=0.243N P=0.281N P=0.234N | |POLY 3 | (e) (e) (e) (e) |P=0.127N P=0.246N P=0.272N P=0.230N | |POLY 1.5 | (e) (e) (e) (e) |P=0.127N P=0.243N P=0.259N P=0.231N | |POLY 6 | (e) (e) (e) (e) |P=0.128N P=0.248N P=0.288N P=0.227N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.099N P=0.218N P=0.109N P=0.328N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.127N P=0.247N P=0.247N P=0.242N | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.027N* (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Deep Cervical | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/39 (0%) 0/49 (0%) 0/42 (0%) 0/38 (0%) |0/32 (0%) 0/31 (0%) 0/34 (0%) 2/41 (5%) | |POLY-3 RATE (b) | 0/36.41 0/45.50 0/38.79 0/34.53 |0/29.03 0/27.22 0/29.03 2/39.35 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 5.1% | |TERMINAL (d) | 0/27 (0%) 0/40 (0%) 0/32 (0%) 0/27 (0%) |0/25 (0%) 0/24 (0%) 0/21 (0%) 2/34 (6%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.078 (e) (e) P=0.308 | |POLY 3 | (e) (e) (e) (e) |P=0.071 (e) (e) P=0.307 | |POLY 1.5 | (e) (e) (e) (e) |P=0.069 (e) (e) P=0.302 | |POLY 6 | (e) (e) (e) (e) |P=0.074 (e) (e) P=0.314 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) P=0.308 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.067 (e) (e) P=0.312 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.066 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 36 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/39 (3%) 0/49 (0%) 3/42 (7%) 1/38 (3%) |5/32 (16%) 3/31 (10%) 2/34 (6%) 7/41 (17%) | |POLY-3 RATE (b) | 1/36.41 0/45.50 3/38.79 1/34.53 |5/29.03 3/27.22 2/29.03 7/39.35 | |POLY-3 PERCENT (g) | 2.8% 0.0% 7.7% 2.9% |17.2% 11.0% 6.9% 17.8% | |TERMINAL (d) | 1/27 (4%) 0/40 (0%) 3/32 (9%) 1/27 (4%) |5/25 (20%) 3/24 (13%) 2/21 (10%) 7/34 (21%) | |FIRST INCIDENCE | 729 (T) --- 729 (T) 729 (T) |729 (T) 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.494 P=0.422N P=0.367 P=0.762 |P=0.424 P=0.374N P=0.285N P=0.606 | |POLY 3 | P=0.500 P=0.455N P=0.328 P=0.749 |P=0.426 P=0.389N P=0.210N P=0.601 | |POLY 1.5 | P=0.505 P=0.455N P=0.328 P=0.751 |P=0.410 P=0.382N P=0.199N P=0.586 | |POLY 6 | P=0.493 P=0.454N P=0.330 P=0.747 |P=0.444 P=0.393N P=0.227N P=0.620 | |LOGISTIC REGRESSION| P=0.494 (e) P=0.367 P=0.762 |P=0.424 P=0.374N P=0.285N P=0.606 | |COCH-ARM / FISHERS | P=0.513 P=0.443N P=0.336 P=0.747 |P=0.384 P=0.372N P=0.189N P=0.564 | |ORDER RESTRICTED | P=0.265 (e) (e) (e) |P=0.365 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/39 (3%) 1/49 (2%) 5/42 (12%) 1/38 (3%) |2/32 (6%) 3/31 (10%) 9/34 (26%) 8/41 (20%) | |POLY-3 RATE (b) | 1/36.41 1/45.50 5/39.28 1/34.53 |2/30.38 3/28.02 9/30.92 8/39.56 | |POLY-3 PERCENT (g) | 2.8% 2.2% 12.7% 2.9% |6.6% 10.7% 29.1% 20.2% | |TERMINAL (d) | 1/27 (4%) 1/40 (3%) 4/32 (13%) 1/27 (4%) |0/25 (0%) 2/24 (8%) 6/21 (29%) 7/34 (21%) | |FIRST INCIDENCE | 729 (T) 729 (T) 583 729 (T) |328 425 496 675 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.589 P=0.672N P=0.136 P=0.762 |P=0.061 P=0.489 P=0.018 * P=0.102 | |POLY 3 | P=0.588 P=0.710N P=0.118 P=0.749 |P=0.066 P=0.463 P=0.021 * P=0.101 | |POLY 1.5 | P=0.595 P=0.710N P=0.117 P=0.751 |P=0.062 P=0.471 P=0.024 * P=0.098 | |POLY 6 | P=0.580 P=0.709N P=0.121 P=0.747 |P=0.072 P=0.457 P=0.018 * P=0.105 | |LOGISTIC REGRESSION| P=0.600 P=0.672N P=0.120 P=0.762 |P=0.023 * P=0.585 P=0.038 * P=0.054 | |COCH-ARM / FISHERS | P=0.605 P=0.693N P=0.118 P=0.747 |P=0.059 P=0.485 P=0.028 * P=0.096 | |ORDER RESTRICTED | P=0.236 (e) (e) (e) |P=0.031 * (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 37 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/39 (5%) 1/49 (2%) 0/42 (0%) 4/38 (11%) |8/32 (25%) 9/31 (29%) 7/34 (21%) 12/41 (29%) | |POLY-3 RATE (b) | 2/36.41 1/45.76 0/38.79 4/34.53 |8/29.03 9/27.93 7/29.14 12/39.38 | |POLY-3 PERCENT (g) | 5.5% 2.2% 0.0% 11.6% |27.6% 32.2% 24.0% 30.5% | |TERMINAL (d) | 2/27 (7%) 0/40 (0%) 0/32 (0%) 4/27 (15%) |8/25 (32%) 8/24 (33%) 6/21 (29%) 11/34 (32%) | |FIRST INCIDENCE | 729 (T) 660 --- 729 (T) |729 (T) 483 701 722 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.069 P=0.410N P=0.201N P=0.334 |P=0.478 P=0.462 P=0.579 P=0.494 | |POLY 3 | P=0.071 P=0.421N P=0.222N P=0.311 |P=0.504 P=0.462 P=0.497N P=0.503 | |POLY 1.5 | P=0.073 P=0.421N P=0.222N P=0.316 |P=0.479 P=0.465 P=0.472N P=0.481 | |POLY 6 | P=0.069 P=0.416N P=0.221N P=0.307 |P=0.534 P=0.464 P=0.532N P=0.530 | |LOGISTIC REGRESSION| P=0.070 P=0.418N (e) P=0.334 |P=0.548N P=0.437 P=0.606N P=0.544 | |COCH-ARM / FISHERS | P=0.076 P=0.414N P=0.229N P=0.325 |P=0.440 P=0.469 P=0.446N P=0.446 | |ORDER RESTRICTED | P=0.054 (e) (e) (e) |P=0.613 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/39 (0%) 1/49 (2%) 0/42 (0%) 1/38 (3%) |1/32 (3%) 0/31 (0%) 2/34 (6%) 0/41 (0%) | |POLY-3 RATE (b) | 0/36.41 1/45.76 0/38.79 1/34.53 |1/29.94 0/27.22 2/29.14 0/39.35 | |POLY-3 PERCENT (g) | 0.0% 2.2% 0.0% 2.9% |3.3% 0.0% 6.9% 0.0% | |TERMINAL (d) | 0/27 (0%) 0/40 (0%) 0/32 (0%) 1/27 (4%) |0/25 (0%) 0/24 (0%) 1/21 (5%) 0/34 (0%) | |FIRST INCIDENCE | --- 660 --- 729 (T) |328 --- 701 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.434 P=0.500 (e) P=0.500 |P=0.452N P=0.500N P=0.447 P=0.500N | |POLY 3 | P=0.427 P=0.546 (e) P=0.489 |P=0.391N P=0.519N P=0.491 P=0.445N | |POLY 1.5 | P=0.429 P=0.545 (e) P=0.491 |P=0.400N P=0.515N P=0.503 P=0.448N | |POLY 6 | P=0.425 P=0.548 (e) P=0.488 |P=0.381N P=0.521N P=0.475 P=0.441N | |LOGISTIC REGRESSION| P=0.440 P=0.589 (e) P=0.500 |P=0.554N (e) P=0.515 (e) | |COCH-ARM / FISHERS | P=0.433 P=0.557 (e) P=0.494 |P=0.413N P=0.508N P=0.523 P=0.438N | |ORDER RESTRICTED | P=0.241 (e) (e) (e) |P=0.264N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 38 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Pancreatic | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/39 (3%) 3/49 (6%) 3/42 (7%) 2/38 (5%) |2/32 (6%) 2/31 (6%) 0/34 (0%) 11/41 (27%) | |POLY-3 RATE (b) | 1/36.41 3/45.50 3/38.93 2/34.53 |2/29.03 2/27.22 0/29.03 11/39.35 | |POLY-3 PERCENT (g) | 2.8% 6.6% 7.7% 5.8% |6.9% 7.4% 0.0% 28.0% | |TERMINAL (d) | 1/27 (4%) 3/40 (8%) 2/32 (6%) 2/27 (7%) |2/25 (8%) 2/24 (8%) 0/21 (0%) 11/34 (32%) | |FIRST INCIDENCE | 729 (T) 729 (T) 694 729 (T) |729 (T) 729 (T) --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.509 P=0.454 P=0.352 P=0.500 |P=0.003 ** P=0.682 P=0.277N P=0.029 * | |POLY 3 | P=0.514 P=0.388 P=0.329 P=0.481 |P<0.001 ** P=0.672 P=0.235N P=0.027 * | |POLY 1.5 | P=0.520 P=0.388 P=0.329 P=0.485 |P<0.001 ** P=0.676 P=0.229N P=0.025 * | |POLY 6 | P=0.508 P=0.391 P=0.332 P=0.479 |P<0.001 ** P=0.670 P=0.245N P=0.030 * | |LOGISTIC REGRESSION| P=0.507 P=0.454 P=0.330 P=0.500 |P=0.003 ** P=0.682 (e) P=0.029 * | |COCH-ARM / FISHERS | P=0.530 P=0.399 P=0.336 P=0.490 |P=0.002 ** P=0.681 P=0.231N P=0.021 * | |ORDER RESTRICTED | P=0.388 (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Pancreatic | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/39 (3%) 0/49 (0%) 1/42 (2%) 4/38 (11%) |5/32 (16%) 3/31 (10%) 2/34 (6%) 9/41 (22%) | |POLY-3 RATE (b) | 1/36.70 0/45.50 1/38.79 4/36.37 |5/30.42 3/27.81 2/29.64 9/39.74 | |POLY-3 PERCENT (g) | 2.7% 0.0% 2.6% 11.0% |16.4% 10.8% 6.8% 22.7% | |TERMINAL (d) | 0/27 (0%) 0/40 (0%) 1/32 (3%) 0/27 (0%) |3/25 (12%) 2/24 (8%) 0/21 (0%) 6/34 (18%) | |FIRST INCIDENCE | 651 --- 729 (T) 491 |328 538 580 675 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.022 * P=0.504N P=0.750N P=0.170 |P=0.159 P=0.381N P=0.293N P=0.342 | |POLY 3 | P=0.015 * P=0.457N P=0.748N P=0.174 |P=0.184 P=0.404N P=0.222N P=0.367 | |POLY 1.5 | P=0.015 * P=0.456N P=0.747N P=0.172 |P=0.177 P=0.394N P=0.208N P=0.359 | |POLY 6 | P=0.015 * P=0.457N P=0.748N P=0.178 |P=0.195 P=0.410N P=0.239N P=0.382 | |LOGISTIC REGRESSION| P=0.020 * P=0.399N P=0.736N P=0.381 |P=0.121 P=0.323N P=0.146N P=0.269 | |COCH-ARM / FISHERS | P=0.015 * P=0.443N P=0.734N P=0.171 |P=0.169 P=0.372N P=0.189N P=0.354 | |ORDER RESTRICTED | P=0.023 * (e) (e) (e) |P=0.135 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 39 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Pancreatic | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 13/39 (33%) 12/49 (24%) 15/42 (36%) 19/38 (50%) |16/32 (50%) 24/31 (77%) 17/34 (50%) 18/41 (44%) | |POLY-3 RATE (b) | 13/36.56 12/46.18 15/38.93 19/35.07 |16/29.46 24/29.56 17/29.53 18/39.82 | |POLY-3 PERCENT (g) | 35.6% 26.0% 38.5% 54.2% |54.3% 81.2% 57.6% 45.2% | |TERMINAL (d) | 11/27 (41%) 10/40 (25%) 14/32 (44%) 18/27 (67%) |15/25 (60%) 20/24 (83%) 16/21 (76%) 16/34 (47%) | |FIRST INCIDENCE | 694 608 694 562 |605 483 580 644 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.010 * P=0.167N P=0.583N P=0.107 |P=0.052N P=0.023 * P=0.208 P=0.329N | |POLY 3 | P=0.012 * P=0.242N P=0.488 P=0.084 |P=0.031N* P=0.021 * P=0.504 P=0.307N | |POLY 1.5 | P=0.014 * P=0.248N P=0.490 P=0.092 |P=0.042N* P=0.020 * P=0.553 P=0.337N | |POLY 6 | P=0.010 * P=0.226N P=0.497 P=0.076 |P=0.020N* P=0.023 * P=0.427 P=0.270N | |LOGISTIC REGRESSION| P=0.010 * P=0.248N P=0.536 P=0.073 |P=0.032N* P=0.015 * P=0.398 P=0.283N | |COCH-ARM / FISHERS | P=0.018 * P=0.249N P=0.504 P=0.105 |P=0.071N P=0.022 * P=0.597N P=0.389N | |ORDER RESTRICTED | P=0.028 * (e) (e) (e) |P=0.031N* (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Lymph Node: Pancreatic | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/39 (3%) 0/49 (0%) 0/42 (0%) 1/38 (3%) |4/32 (13%) 2/31 (6%) 0/34 (0%) 1/41 (2%) | |POLY-3 RATE (b) | 1/36.41 0/45.50 0/38.79 1/35.22 |4/30.84 2/28.14 0/29.03 1/39.38 | |POLY-3 PERCENT (g) | 2.8% 0.0% 0.0% 2.8% |13.0% 7.1% 0.0% 2.5% | |TERMINAL (d) | 1/27 (4%) 0/40 (0%) 0/32 (0%) 0/27 (0%) |1/25 (4%) 0/24 (0%) 0/21 (0%) 0/34 (0%) | |FIRST INCIDENCE | 729 (T) --- --- 491 |328 538 --- 722 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.513 P=0.422N P=0.466N P=0.758 |P=0.085N P=0.359N P=0.085N P=0.157N | |POLY 3 | P=0.508 P=0.455N P=0.487N P=0.753 |P=0.051N P=0.379N P=0.065N P=0.110N | |POLY 1.5 | P=0.508 P=0.455N P=0.487N P=0.754 |P=0.052N P=0.369N P=0.058N P=0.110N | |POLY 6 | P=0.506 P=0.454N P=0.486N P=0.753 |P=0.051N P=0.384N P=0.074N P=0.109N | |LOGISTIC REGRESSION| P=0.557 (e) (e) P=0.631N |P=0.089N P=0.220N P=0.026N* P=0.185N | |COCH-ARM / FISHERS | P=0.508 P=0.443N P=0.481N P=0.747 |P=0.055N P=0.351N P=0.050N P=0.112N | |ORDER RESTRICTED | P=0.373 (e) (e) (e) |P=0.019N* (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 40 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Mammary Gland | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/48 (15%) 1/47 (2%) 3/45 (7%) 2/42 (5%) |33/50 (66%) 35/50 (70%) 22/50 (44%) 19/50 (38%) | |POLY-3 RATE (b) | 7/45.50 1/44.02 3/41.06 2/36.97 |33/46.32 35/45.74 22/41.65 19/48.36 | |POLY-3 PERCENT (g) | 15.4% 2.3% 7.3% 5.4% |71.2% 76.5% 52.8% 39.3% | |TERMINAL (d) | 3/34 (9%) 1/39 (3%) 2/34 (6%) 2/30 (7%) |31/40 (78%) 32/39 (82%) 17/28 (61%) 17/42 (41%) | |FIRST INCIDENCE | 689 729 (T) 694 729 (T) |671 598 665 644 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.243N P=0.029N* P=0.173N P=0.114N |P<0.001N** P=0.332 P=0.441N P=0.002N** | |POLY 3 | P=0.253N P=0.033N* P=0.202N P=0.138N |P<0.001N** P=0.361 P=0.050N P<0.001N** | |POLY 1.5 | P=0.247N P=0.033N* P=0.196N P=0.131N |P<0.001N** P=0.381 P=0.035N* P=0.002N** | |POLY 6 | P=0.260N P=0.033N* P=0.205N P=0.144N |P<0.001N** P=0.357 P=0.076N P<0.001N** | |LOGISTIC REGRESSION| P=0.259N P=0.035N* P=0.196N P=0.135N |P<0.001N** P=0.322 P=0.177N P<0.001N** | |COCH-ARM / FISHERS | P=0.232N P=0.032N* P=0.186N P=0.115N |P<0.001N** P=0.415 P=0.022N* P=0.004N** | |ORDER RESTRICTED | P=0.058N (e) (e) (e) |P<0.001N** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Mammary Gland | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 1/45 (2%) 0/42 (0%) |2/50 (4%) 3/50 (6%) 7/50 (14%) 0/50 (0%) | |POLY-3 RATE (b) | 0/45.05 0/44.02 1/41.50 0/36.97 |2/46.54 3/46.72 7/44.02 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.4% 0.0% |4.3% 6.4% 15.9% 0.0% | |TERMINAL (d) | 0/34 (0%) 0/39 (0%) 0/34 (0%) 0/30 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- --- 548 --- |653 425 496 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.789N (e) P=0.487 (e) |P=0.265N P=0.492 P=0.061 P=0.223N | |POLY 3 | P=0.794 (e) P=0.484 (e) |P=0.250N P=0.502 P=0.066 P=0.230N | |POLY 1.5 | P=0.799 (e) P=0.484 (e) |P=0.259N P=0.502 P=0.070 P=0.233N | |POLY 6 | P=0.791 (e) P=0.485 (e) |P=0.241N P=0.502 P=0.061 P=0.228N | |LOGISTIC REGRESSION| P=0.656N (e) P=0.790 (e) |P=0.326N P=0.563 P=0.164 P=0.274N | |COCH-ARM / FISHERS | P=0.805N (e) P=0.484 (e) |P=0.277N P=0.500 P=0.080 P=0.247N | |ORDER RESTRICTED | P=0.370 (e) (e) (e) |P=0.054N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 41 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 0/47 (0%) 0/45 (0%) 0/42 (0%) |3/50 (6%) 5/50 (10%) 4/50 (8%) 3/50 (6%) | |POLY-3 RATE (b) | 2/45.05 0/44.02 0/40.93 0/36.97 |3/46.87 5/45.18 4/41.34 3/48.02 | |POLY-3 PERCENT (g) | 4.4% 0.0% 0.0% 0.0% |6.4% 11.1% 9.7% 6.3% | |TERMINAL (d) | 2/34 (6%) 0/39 (0%) 0/34 (0%) 0/30 (0%) |1/40 (3%) 4/39 (10%) 3/28 (11%) 3/42 (7%) | |FIRST INCIDENCE | 729 (T) --- --- --- |588 680 548 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.268N P=0.209N P=0.238N P=0.266N |P=0.449N P=0.347 P=0.364 P=0.637N | |POLY 3 | P=0.261N P=0.242N P=0.259N P=0.283N |P=0.451N P=0.337 P=0.432 P=0.651N | |POLY 1.5 | P=0.260N P=0.243N P=0.257N P=0.279N |P=0.457N P=0.345 P=0.459 P=0.655N | |POLY 6 | P=0.262N P=0.240N P=0.259N P=0.284N |P=0.445N P=0.329 P=0.398 P=0.646N | |LOGISTIC REGRESSION| P=0.268N (e) (e) (e) |P=0.464N P=0.362 P=0.544 P=0.626 | |COCH-ARM / FISHERS | P=0.261N P=0.253N P=0.264N P=0.282N |P=0.465N P=0.357 P=0.500 P=0.661N | |ORDER RESTRICTED | P=0.049N* (e) (e) (e) |P=0.489N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/47 (0%) 0/45 (0%) 1/42 (2%) |1/50 (2%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | 0/45.05 0/44.02 0/40.93 1/37.12 |1/46.43 0/44.99 2/41.64 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.7% |2.2% 0.0% 4.8% 0.0% | |TERMINAL (d) | 0/34 (0%) 0/39 (0%) 0/34 (0%) 0/30 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- --- --- 689 |602 --- 598 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.205 (e) (e) P=0.485 |P=0.471N P=0.513N P=0.450 P=0.492N | |POLY 3 | P=0.187 (e) (e) P=0.461 |P=0.466N P=0.506N P=0.462 P=0.493N | |POLY 1.5 | P=0.189 (e) (e) P=0.464 |P=0.473N P=0.504N P=0.477 P=0.496N | |POLY 6 | P=0.186 (e) (e) P=0.461 |P=0.458N P=0.508N P=0.445 P=0.490N | |LOGISTIC REGRESSION| P=0.201 (e) (e) P=0.484 |P=0.517N P=0.497N P=0.612 P=0.577N | |COCH-ARM / FISHERS | P=0.195 (e) (e) P=0.467 |P=0.485N P=0.500N P=0.500 P=0.500N | |ORDER RESTRICTED | P=0.093 (e) (e) (e) |P=0.301N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 42 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Mesentery | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/26 (0%) 0/46 (0%) 0/35 (0%) 2/20 (10%) |0/8 (0%) 0/10 (0%) 0/12 (0%) 0/9 (0%) | |POLY-3 RATE (b) | 0/23.45 0/43.82 0/32.63 2/18.53 |0/7.19 0/9.03 0/9.00 0/8.21 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 10.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/40 (0%) 0/27 (0%) 1/13 (8%) |0/5 (0%) 0/7 (0%) 0/4 (0%) 0/8 (0%) | |FIRST INCIDENCE | --- --- --- 249 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.019 * (e) (e) P=0.226 |(e) (e) (e) (e) | |POLY 3 | P=0.008 ** (e) (e) P=0.181 |(e) (e) (e) (e) | |POLY 1.5 | P=0.008 ** (e) (e) P=0.179 |(e) (e) (e) (e) | |POLY 6 | P=0.007 ** (e) (e) P=0.185 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.060 (e) (e) P=0.365 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.009 ** (e) (e) P=0.184 |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.015 * (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/26 (4%) 1/46 (2%) 2/35 (6%) 0/20 (0%) |0/8 (0%) 1/10 (10%) 2/12 (17%) 0/9 (0%) | |POLY-3 RATE (b) | 1/23.74 1/44.46 2/33.96 0/17.57 |0/7.19 1/9.36 2/10.07 0/8.21 | |POLY-3 PERCENT (g) | 4.2% 2.3% 5.9% 0.0% |0.0% 10.7% 19.9% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/40 (0%) 0/27 (0%) 0/13 (0%) |0/5 (0%) 0/7 (0%) 0/4 (0%) 0/8 (0%) | |FIRST INCIDENCE | 651 521 392 --- |--- 638 548 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.350N P=0.756 P=0.482 P=0.519N |P=0.593N P=0.495 P=0.214 (e) | |POLY 3 | P=0.497N P=0.614N P=0.623 P=0.560N |P=0.592N P=0.552 P=0.305 (e) | |POLY 1.5 | P=0.491N P=0.621N P=0.614 P=0.559N |P=0.597N P=0.549 P=0.314 (e) | |POLY 6 | P=0.504N P=0.603N P=0.636 P=0.559N |P=0.575N P=0.558 P=0.293 (e) | |LOGISTIC REGRESSION| P=0.111N P=0.639N P=0.671 P=0.521N |P=0.394N P=0.521 P=0.729 (e) | |COCH-ARM / FISHERS | P=0.474N P=0.595N P=0.612 P=0.565N |P=0.594N P=0.556 P=0.347 (e) | |ORDER RESTRICTED | P=0.433N (e) (e) (e) |P=0.368N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 43 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/26 (31%) 10/46 (22%) 16/35 (46%) 10/20 (50%) |5/8 (63%) 7/10 (70%) 6/12 (50%) 3/9 (33%) | |POLY-3 RATE (b) | 8/23.90 10/43.82 16/33.31 10/17.88 |5/7.19 7/9.03 6/9.46 3/8.21 | |POLY-3 PERCENT (g) | 33.5% 22.8% 48.0% 55.9% |69.6% 77.5% 63.4% 36.5% | |TERMINAL (d) | 5/15 (33%) 10/40 (25%) 12/27 (44%) 8/13 (62%) |5/5 (100%) 7/7 (100%) 3/4 (75%) 3/8 (38%) | |FIRST INCIDENCE | 668 729 (T) 668 689 |729 (T) 729 (T) 665 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.041 * P=0.134N P=0.290 P=0.276 |P=0.023N* P=1.000N P=0.261 P=0.055N | |POLY 3 | P=0.015 * P=0.256N P=0.203 P=0.124 |P=0.058N P=0.587 P=0.610N P=0.213N | |POLY 1.5 | P=0.017 * P=0.270N P=0.188 P=0.128 |P=0.077N P=0.575 P=0.541N P=0.232N | |POLY 6 | P=0.013 * P=0.232N P=0.236 P=0.126 |P=0.028N* P=0.612 P=0.711N P=0.173N | |LOGISTIC REGRESSION| P=0.015 * P=0.186N P=0.216 P=0.140 |P=0.020N* P=1.000N P=0.471 P=0.055N | |COCH-ARM / FISHERS | P=0.027 * P=0.283N P=0.180 P=0.154 |P=0.088N P=0.563 P=0.465N P=0.238N | |ORDER RESTRICTED | P=0.076 (e) (e) (e) |P=0.097N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Nose | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |1/50 (2%) 1/49 (2%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 2/46.18 0/45.93 1/44.49 0/43.91 |1/46.00 1/44.59 0/40.77 2/48.05 | |POLY-3 PERCENT (g) | 4.3% 0.0% 2.3% 0.0% |2.2% 2.2% 0.0% 4.2% | |TERMINAL (d) | 1/35 (3%) 0/40 (0%) 1/36 (3%) 0/35 (0%) |1/40 (3%) 1/39 (3%) 0/28 (0%) 1/42 (2%) | |FIRST INCIDENCE | 716 --- 729 (T) --- |729 (T) 729 (T) --- 722 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.286N P=0.220N P=0.497N P=0.249N |P=0.385 P=0.756 P=0.571N P=0.522 | |POLY 3 | P=0.279N P=0.238N P=0.513N P=0.249N |P=0.378 P=0.754 P=0.524N P=0.515 | |POLY 1.5 | P=0.277N P=0.238N P=0.508N P=0.245N |P=0.375 P=0.754 P=0.515N P=0.509 | |POLY 6 | P=0.281N P=0.238N P=0.516N P=0.252N |P=0.382 P=0.754 P=0.536N P=0.523 | |LOGISTIC REGRESSION| P=0.285N P=0.237N P=0.513N P=0.251N |P=0.394 P=0.756 (e) P=0.530 | |COCH-ARM / FISHERS | P=0.271N P=0.247N P=0.500N P=0.247N |P=0.371 P=0.747 P=0.500N P=0.500 | |ORDER RESTRICTED | P=0.081N (e) (e) (e) |P=0.299 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 44 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Nose: Nasolacrimal Duct | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 5/50 (10%) 1/50 (2%) 2/50 (4%) |4/50 (8%) 2/49 (4%) 4/50 (8%) 0/50 (0%) | |POLY-3 RATE (b) | 0/46.13 5/46.80 1/44.49 2/43.91 |4/46.00 2/44.59 4/40.77 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 10.7% 2.3% 4.6% |8.7% 4.5% 9.8% 0.0% | |TERMINAL (d) | 0/35 (0%) 3/40 (8%) 1/36 (3%) 2/35 (6%) |4/40 (10%) 2/39 (5%) 4/28 (14%) 0/42 (0%) | |FIRST INCIDENCE | --- 507 729 (T) 729 (T) |729 (T) 729 (T) 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.609 P=0.043 * P=0.506 P=0.238 |P=0.089N P=0.348N P=0.438 P=0.057N | |POLY 3 | P=0.612 P=0.032 * P=0.493 P=0.226 |P=0.072N P=0.352N P=0.576 P=0.055N | |POLY 1.5 | P=0.620 P=0.032 * P=0.495 P=0.230 |P=0.076N P=0.350N P=0.602 P=0.057N | |POLY 6 | P=0.606 P=0.032 * P=0.491 P=0.223 |P=0.067N P=0.351N P=0.541 P=0.053N | |LOGISTIC REGRESSION| P=0.606N P=0.030 * P=0.506 P=0.238 |P=0.089N P=0.348N P=0.438 (e) | |COCH-ARM / FISHERS | P=0.609N P=0.028 * P=0.500 P=0.247 |P=0.083N P=0.349N P=0.643N P=0.059N | |ORDER RESTRICTED | P=0.131 (e) (e) (e) |P=0.041N* (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |5/50 (10%) 5/49 (10%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | |5/47.78 5/45.30 2/40.77 0/48.02 | |POLY-3 PERCENT (g) | |10.5% 11.0% 4.9% 0.0% | |TERMINAL (d) | |2/40 (5%) 4/39 (10%) 2/28 (7%) 0/42 (0%) | |FIRST INCIDENCE | |328 483 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.015N* P=0.612 P=0.331N P=0.033N* | |POLY 3 | |P=0.012N* P=0.596 P=0.286N P=0.030N* | |POLY 1.5 | |P=0.012N* P=0.603 P=0.258N P=0.031N* | |POLY 6 | |P=0.011N* P=0.591 P=0.321N P=0.030N* | |LOGISTIC REGRESSION| |P=0.011N* P=0.615N P=0.135N P=0.046N* | |COCH-ARM / FISHERS | |P=0.012N* P=0.617 P=0.218N P=0.028N* | |ORDER RESTRICTED | |P=0.019N* (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 45 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Ovary: Periovarian Tissue | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |5/50 (10%) 5/49 (10%) 4/50 (8%) 6/50 (12%) | |POLY-3 RATE (b) | |5/46.42 5/45.04 4/41.56 6/48.15 | |POLY-3 PERCENT (g) | |10.8% 11.1% 9.6% 12.5% | |TERMINAL (d) | |4/40 (10%) 4/39 (10%) 2/28 (7%) 5/42 (12%) | |FIRST INCIDENCE | |605 598 496 696 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.461 P=0.610 P=0.599 P=0.537 | |POLY 3 | |P=0.463 P=0.611 P=0.569N P=0.525 | |POLY 1.5 | |P=0.455 P=0.613 P=0.542N P=0.516 | |POLY 6 | |P=0.474 P=0.612 P=0.603N P=0.538 | |LOGISTIC REGRESSION| |P=0.450 P=0.617 P=0.503N P=0.514 | |COCH-ARM / FISHERS | |P=0.443 P=0.617 P=0.500N P=0.500 | |ORDER RESTRICTED | |P=0.593 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 22/49 (45%) 27/49 (55%) 20/50 (40%) 36/50 (72%) |13/50 (26%) 14/49 (29%) 13/49 (27%) 11/50 (22%) | |POLY-3 RATE (b) | 22/46.91 27/45.98 20/45.66 36/47.35 |13/47.38 14/44.59 13/42.12 11/48.36 | |POLY-3 PERCENT (g) | 46.9% 58.7% 43.8% 76.0% |27.4% 31.4% 30.9% 22.8% | |TERMINAL (d) | 13/35 (37%) 24/40 (60%) 16/36 (44%) 26/35 (74%) |11/40 (28%) 14/39 (36%) 8/28 (29%) 9/42 (21%) | |FIRST INCIDENCE | 603 660 538 395 |328 729 (T) 526 644 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.003 ** P=0.386 P=0.417N P=0.012 * |P=0.296N P=0.468 P=0.264 P=0.359N | |POLY 3 | P=0.003 ** P=0.173 P=0.464N P=0.002 ** |P=0.278N P=0.426 P=0.451 P=0.385N | |POLY 1.5 | P=0.003 ** P=0.191 P=0.431N P=0.003 ** |P=0.294N P=0.442 P=0.491 P=0.397N | |POLY 6 | P=0.002 ** P=0.153 P=0.500N P=0.002 ** |P=0.254N P=0.415 P=0.409 P=0.365N | |LOGISTIC REGRESSION| P=0.002 ** P=0.209 P=0.425N P=0.004 ** |P=0.291N P=0.469 P=0.564 P=0.439N | |COCH-ARM / FISHERS | P=0.005 ** P=0.210 P=0.386N P=0.005 ** |P=0.309N P=0.475 P=0.567 P=0.408N | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P=0.340N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 46 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pancreas: Duct | | Cyst Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/49 (12%) 3/49 (6%) 5/50 (10%) 12/50 (24%) |10/50 (20%) 12/49 (24%) 4/49 (8%) 6/50 (12%) | |POLY-3 RATE (b) | 6/45.56 3/45.49 5/44.49 12/44.46 |10/46.00 12/45.04 4/40.34 6/48.02 | |POLY-3 PERCENT (g) | 13.2% 6.6% 11.2% 27.0% |21.7% 26.6% 9.9% 12.5% | |TERMINAL (d) | 4/35 (11%) 2/40 (5%) 5/36 (14%) 10/35 (29%) |10/40 (25%) 11/39 (28%) 4/28 (14%) 6/42 (14%) | |FIRST INCIDENCE | 651 693 729 (T) 598 |729 (T) 598 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.007 ** P=0.208N P=0.490N P=0.095 |P=0.063N P=0.376 P=0.222N P=0.174N | |POLY 3 | P=0.008 ** P=0.243N P=0.517N P=0.083 |P=0.055N P=0.382 P=0.115N P=0.179N | |POLY 1.5 | P=0.008 ** P=0.242N P=0.505N P=0.089 |P=0.058N P=0.382 P=0.100N P=0.190N | |POLY 6 | P=0.007 ** P=0.242N P=0.527N P=0.077 |P=0.051N P=0.388 P=0.137N P=0.166N | |LOGISTIC REGRESSION| P=0.007 ** P=0.240N P=0.514N P=0.084 |P=0.051N P=0.373 P=0.222N P=0.174N | |COCH-ARM / FISHERS | P=0.011 * P=0.243N P=0.486N P=0.104 |P=0.064N P=0.384 P=0.080N P=0.207N | |ORDER RESTRICTED | P=0.012 * (e) (e) (e) |P=0.068N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pancreas: Duct | | Hyperplasia Cystic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 2/49 (4%) 3/50 (6%) 0/50 (0%) |0/50 (0%) 0/49 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/45.14 2/45.35 3/44.49 0/43.91 |0/46.00 0/44.59 0/40.34 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 4.4% 6.7% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 2/40 (5%) 3/36 (8%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 729 (T) 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.401N P=0.268 P=0.126 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.399N P=0.238 P=0.116 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.391N P=0.238 P=0.118 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.405N P=0.239 P=0.114 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.268 P=0.126 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.375N P=0.247 P=0.125 (e) |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.223 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 47 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Parathyroid Gland | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/47 (4%) 0/49 (0%) 1/48 (2%) 0/49 (0%) |0/49 (0%) 0/48 (0%) 0/49 (0%) 0/47 (0%) | |POLY-3 RATE (b) | 2/43.42 0/44.93 1/42.72 0/42.91 |0/45.00 0/43.70 0/40.10 0/45.81 | |POLY-3 PERCENT (g) | 4.6% 0.0% 2.3% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/33 (3%) 0/39 (0%) 1/35 (3%) 0/34 (0%) |0/39 (0%) 0/39 (0%) 0/28 (0%) 0/40 (0%) | |FIRST INCIDENCE | 694 --- 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.283N P=0.224N P=0.489N P=0.248N |(e) (e) (e) (e) | |POLY 3 | P=0.273N P=0.229N P=0.506N P=0.240N |(e) (e) (e) (e) | |POLY 1.5 | P=0.271N P=0.228N P=0.501N P=0.236N |(e) (e) (e) (e) | |POLY 6 | P=0.276N P=0.230N P=0.509N P=0.244N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.277N P=0.229N P=0.505N P=0.237N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.266N P=0.237N P=0.492N P=0.237N |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.076N (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 3/50 (6%) 0/50 (0%) |5/50 (10%) 9/48 (19%) 7/50 (14%) 2/50 (4%) | |POLY-3 RATE (b) | 2/46.41 0/45.93 3/44.63 0/43.91 |5/46.00 9/44.69 7/42.17 2/48.02 | |POLY-3 PERCENT (g) | 4.3% 0.0% 6.7% 0.0% |10.9% 20.1% 16.6% 4.2% | |TERMINAL (d) | 1/35 (3%) 0/40 (0%) 2/36 (6%) 0/35 (0%) |5/40 (13%) 7/39 (18%) 3/28 (11%) 2/42 (5%) | |FIRST INCIDENCE | 651 --- 694 --- |729 (T) 425 548 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.319N P=0.227N P=0.499 P=0.250N |P=0.099N P=0.184 P=0.201 P=0.197N | |POLY 3 | P=0.315N P=0.240N P=0.482 P=0.250N |P=0.075N P=0.176 P=0.319 P=0.199N | |POLY 1.5 | P=0.309N P=0.238N P=0.489 P=0.245N |P=0.081N P=0.174 P=0.341 P=0.206N | |POLY 6 | P=0.321N P=0.240N P=0.478 P=0.254N |P=0.068N P=0.180 P=0.294 P=0.191N | |LOGISTIC REGRESSION| P=0.304N P=0.239N P=0.492 P=0.233N |P=0.090N P=0.170 P=0.345 P=0.197N | |COCH-ARM / FISHERS | P=0.297N P=0.247N P=0.500 P=0.247N |P=0.091N P=0.172 P=0.380 P=0.218N | |ORDER RESTRICTED | P=0.162N (e) (e) (e) |P=0.059N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 48 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 2/50 (4%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 0/48 (0%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 3/46.14 2/45.93 2/44.49 1/44.07 |0/46.00 0/43.78 0/40.77 1/48.02 | |POLY-3 PERCENT (g) | 6.5% 4.4% 4.5% 2.3% |0.0% 0.0% 0.0% 2.1% | |TERMINAL (d) | 2/35 (6%) 2/40 (5%) 2/36 (6%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 1/42 (2%) | |FIRST INCIDENCE | 726 729 (T) 729 (T) 687 |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.289N P=0.442N P=0.490N P=0.313N |P=0.208 (e) (e) P=0.510 | |POLY 3 | P=0.284N P=0.502N P=0.517N P=0.322N |P=0.203 (e) (e) P=0.509 | |POLY 1.5 | P=0.280N P=0.501N P=0.510N P=0.317N |P=0.201 (e) (e) P=0.505 | |POLY 6 | P=0.288N P=0.502N P=0.520N P=0.325N |P=0.206 (e) (e) P=0.513 | |LOGISTIC REGRESSION| P=0.292N P=0.469N P=0.505N P=0.325N |(e) (e) (e) P=0.510 | |COCH-ARM / FISHERS | P=0.269N P=0.500N P=0.500N P=0.309N |P=0.196 (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.263N (e) (e) (e) |P=0.129 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 4/50 (8%) 2/50 (4%) 3/50 (6%) |1/50 (2%) 5/48 (10%) 2/50 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 1/46.13 4/45.93 2/44.49 3/43.91 |1/46.00 5/43.78 2/41.10 1/48.15 | |POLY-3 PERCENT (g) | 2.2% 8.7% 4.5% 6.8% |2.2% 11.4% 4.9% 2.1% | |TERMINAL (d) | 1/35 (3%) 4/40 (10%) 2/36 (6%) 3/35 (9%) |1/40 (3%) 5/39 (13%) 1/28 (4%) 0/42 (0%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |729 (T) 729 (T) 638 696 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.419 P=0.221 P=0.510 P=0.305 |P=0.296N P=0.097 P=0.404 P=0.745N | |POLY 3 | P=0.424 P=0.177 P=0.487 P=0.288 |P=0.279N P=0.090 P=0.461 P=0.750N | |POLY 1.5 | P=0.433 P=0.179 P=0.492 P=0.294 |P=0.286N P=0.091 P=0.476 P=0.754N | |POLY 6 | P=0.416 P=0.177 P=0.485 P=0.283 |P=0.270N P=0.090 P=0.442 P=0.745N | |LOGISTIC REGRESSION| P=0.419 P=0.221 P=0.510 P=0.305 |P=0.285N P=0.097 P=0.476 P=0.762N | |COCH-ARM / FISHERS | P=0.450 P=0.181 P=0.500 P=0.309 |P=0.295N P=0.093 P=0.500 P=0.753N | |ORDER RESTRICTED | P=0.267 (e) (e) (e) |P=0.231N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 49 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cytoplasmic Alteration Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 4/50 (8%) 2/50 (4%) 5/50 (10%) |4/50 (8%) 4/48 (8%) 1/50 (2%) 3/50 (6%) | |POLY-3 RATE (b) | 1/46.13 4/47.79 2/44.49 5/44.36 |4/46.47 4/43.78 1/40.77 3/48.02 | |POLY-3 PERCENT (g) | 2.2% 8.4% 4.5% 11.3% |8.6% 9.1% 2.5% 6.3% | |TERMINAL (d) | 1/35 (3%) 0/40 (0%) 2/36 (6%) 4/35 (11%) |3/40 (8%) 4/39 (10%) 1/28 (4%) 3/42 (7%) | |FIRST INCIDENCE | 729 (T) 507 729 (T) 598 |588 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.122 P=0.189 P=0.510 P=0.102 |P=0.328N P=0.626 P=0.287N P=0.476N | |POLY 3 | P=0.122 P=0.190 P=0.487 P=0.092 |P=0.323N P=0.610 P=0.221N P=0.482N | |POLY 1.5 | P=0.127 P=0.186 P=0.492 P=0.095 |P=0.324N P=0.614 P=0.204N P=0.489N | |POLY 6 | P=0.118 P=0.196 P=0.485 P=0.090 |P=0.320N P=0.609 P=0.244N P=0.474N | |LOGISTIC REGRESSION| P=0.165 P=0.138 P=0.510 P=0.096 |P=0.309N P=0.618 P=0.199N P=0.503N | |COCH-ARM / FISHERS | P=0.137 P=0.181 P=0.500 P=0.102 |P=0.325N P=0.619 P=0.181N P=0.500N | |ORDER RESTRICTED | P=0.060 (e) (e) (e) |P=0.305N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Degeneration Cystic Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 1/50 (2%) 1/50 (2%) |9/50 (18%) 14/48 (29%) 8/50 (16%) 5/50 (10%) | |POLY-3 RATE (b) | 1/46.13 1/46.50 1/44.49 1/43.91 |9/46.87 14/44.49 8/42.00 5/48.15 | |POLY-3 PERCENT (g) | 2.2% 2.2% 2.3% 2.3% |19.2% 31.5% 19.1% 10.4% | |TERMINAL (d) | 1/35 (3%) 0/40 (0%) 1/36 (3%) 1/35 (3%) |7/40 (18%) 13/39 (33%) 6/28 (21%) 4/42 (10%) | |FIRST INCIDENCE | 729 (T) 548 729 (T) 729 (T) |588 483 332 696 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.653 P=0.748N P=0.756N P=0.762 |P=0.058N P=0.156 P=0.447 P=0.172N | |POLY 3 | P=0.648 P=0.759N P=0.753 P=0.750 |P=0.044N* P=0.133 P=0.599N P=0.178N | |POLY 1.5 | P=0.654 P=0.759N P=0.755 P=0.753 |P=0.046N* P=0.137 P=0.558N P=0.184N | |POLY 6 | P=0.642 P=0.757N P=0.751 P=0.747 |P=0.041N* P=0.129 P=0.560 P=0.171N | |LOGISTIC REGRESSION| P=0.655N P=0.745 P=0.756N P=0.762 |P=0.051N P=0.141 P=0.500N P=0.195N | |COCH-ARM / FISHERS | P=0.667 P=0.753N P=0.753N P=0.753N |P=0.052N P=0.143 P=0.500N P=0.194N | |ORDER RESTRICTED | P=0.731 (e) (e) (e) |P=0.043N* (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 50 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hemorrhage Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 3/48 (6%) 4/50 (8%) 6/50 (12%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 0/43.91 |1/46.00 3/43.78 4/42.06 6/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.2% 6.9% 9.5% 12.5% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |1/40 (3%) 3/39 (8%) 1/28 (4%) 6/42 (14%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 729 (T) 532 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.050 P=0.296 P=0.123 P=0.066 | |POLY 3 | (e) (e) (e) (e) |P=0.047 * P=0.288 P=0.152 P=0.063 | |POLY 1.5 | (e) (e) (e) (e) |P=0.044 * P=0.289 P=0.162 P=0.061 | |POLY 6 | (e) (e) (e) (e) |P=0.050 P=0.289 P=0.141 P=0.067 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.042 * P=0.296 P=0.220 P=0.066 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.041 * P=0.293 P=0.181 P=0.056 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.038 * (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 0/50 (0%) 2/50 (4%) |1/50 (2%) 1/48 (2%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 2/46.41 1/45.93 0/44.49 2/44.45 |1/46.00 1/43.78 1/40.77 1/48.05 | |POLY-3 PERCENT (g) | 4.3% 2.2% 0.0% 4.5% |2.2% 2.3% 2.5% 2.1% | |TERMINAL (d) | 0/35 (0%) 1/40 (3%) 0/36 (0%) 1/35 (3%) |1/40 (3%) 1/39 (3%) 1/28 (4%) 0/42 (0%) | |FIRST INCIDENCE | 668 729 (T) --- 562 |729 (T) 729 (T) 729 (T) 722 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.490 P=0.481N P=0.248N P=0.674 |P=0.615N P=0.756 P=0.680 P=0.744N | |POLY 3 | P=0.502 P=0.504N P=0.247N P=0.678 |P=0.619N P=0.750 P=0.733 P=0.751N | |POLY 1.5 | P=0.504 P=0.502N P=0.243N P=0.683 |P=0.622N P=0.750 P=0.744 P=0.755N | |POLY 6 | P=0.499 P=0.505N P=0.250N P=0.674 |P=0.616N P=0.750 P=0.719 P=0.746N | |LOGISTIC REGRESSION| P=0.531 P=0.500N P=0.234N P=0.673N |P=0.606N P=0.756 P=0.680 P=0.745N | |COCH-ARM / FISHERS | P=0.512 P=0.500N P=0.247N P=0.691N |P=0.626N P=0.742 P=0.753N P=0.753N | |ORDER RESTRICTED | P=0.399 (e) (e) (e) |P=0.714N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 51 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Pars Intermedia | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/48 (0%) 1/50 (2%) 3/50 (6%) | |POLY-3 RATE (b) | 0/46.13 2/46.18 0/44.49 1/43.91 |0/46.00 0/43.78 1/41.39 3/48.02 | |POLY-3 PERCENT (g) | 0.0% 4.3% 0.0% 2.3% |0.0% 0.0% 2.4% 6.3% | |TERMINAL (d) | 0/35 (0%) 1/40 (3%) 0/36 (0%) 1/35 (3%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 3/42 (7%) | |FIRST INCIDENCE | --- 660 --- 729 (T) |--- --- 526 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.606 P=0.254 (e) P=0.500 |P=0.024 * (e) P=0.492 P=0.130 | |POLY 3 | P=0.609 P=0.237 (e) P=0.490 |P=0.021 * (e) P=0.479 P=0.127 | |POLY 1.5 | P=0.613 P=0.238 (e) P=0.493 |P=0.020 * (e) P=0.487 P=0.124 | |POLY 6 | P=0.605 P=0.238 (e) P=0.487 |P=0.022 * (e) P=0.469 P=0.131 | |LOGISTIC REGRESSION| P=0.616 P=0.237 (e) P=0.500 |P=0.017 * (e) P=0.615 P=0.130 | |COCH-ARM / FISHERS | P=0.622 P=0.247 (e) P=0.500 |P=0.020 * (e) P=0.500 P=0.121 | |ORDER RESTRICTED | P=0.316 (e) (e) (e) |P=0.024 * (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Pituitary Gland: Rathke's Cleft | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/48 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 0/43.91 |0/46.00 0/43.78 0/40.77 2/48.23 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 4.2% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 1/42 (2%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 675 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.057 (e) (e) P=0.260 | |POLY 3 | (e) (e) (e) (e) |P=0.047 * (e) (e) P=0.248 | |POLY 1.5 | (e) (e) (e) (e) |P=0.046 * (e) (e) P=0.244 | |POLY 6 | (e) (e) (e) (e) |P=0.048 * (e) (e) P=0.254 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.047 * (e) (e) P=0.229 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.046 * (e) (e) P=0.247 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.033 * (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 52 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Preputial Gland | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 2/44.34 | | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.5% | | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 1/35 (3%) | | |FIRST INCIDENCE | --- --- --- 605 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.037 * (e) (e) P=0.230 | | |POLY 3 | P=0.039 * (e) (e) P=0.228 | | |POLY 1.5 | P=0.039 * (e) (e) P=0.231 | | |POLY 6 | P=0.038 * (e) (e) P=0.227 | | |LOGISTIC REGRESSION| P=0.047 * (e) (e) P=0.251 | | |COCH-ARM / FISHERS | P=0.042 * (e) (e) P=0.247 | | |ORDER RESTRICTED | P=0.026 * (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Preputial Gland | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 2/50 (4%) 1/50 (2%) | | |POLY-3 RATE (b) | 2/46.13 0/45.93 2/44.59 1/44.07 | | |POLY-3 PERCENT (g) | 4.3% 0.0% 4.5% 2.3% | | |TERMINAL (d) | 2/35 (6%) 0/40 (0%) 1/36 (3%) 0/35 (0%) | | |FIRST INCIDENCE | 729 (T) --- 703 687 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.614N P=0.209N P=0.686N P=0.503N | | |POLY 3 | P=0.610N P=0.238N P=0.682 P=0.516N | | |POLY 1.5 | P=0.606N P=0.238N P=0.686 P=0.511N | | |POLY 6 | P=0.613N P=0.238N P=0.680 P=0.519N | | |LOGISTIC REGRESSION| P=0.614N (e) P=0.681 P=0.518N | | |COCH-ARM / FISHERS | P=0.596N P=0.247N P=0.691N P=0.500N | | |ORDER RESTRICTED | P=0.430N (e) (e) (e) | | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 53 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Preputial Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 2/50 (4%) | | |POLY-3 RATE (b) | 0/46.13 1/45.93 1/44.63 2/44.23 | | |POLY-3 PERCENT (g) | 0.0% 2.2% 2.2% 4.5% | | |TERMINAL (d) | 0/35 (0%) 1/40 (3%) 0/36 (0%) 0/35 (0%) | | |FIRST INCIDENCE | --- 729 (T) 694 687 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.183 P=0.527 P=0.495 P=0.232 | | |POLY 3 | P=0.184 P=0.499 P=0.493 P=0.228 | | |POLY 1.5 | P=0.187 P=0.500 P=0.496 P=0.231 | | |POLY 6 | P=0.182 P=0.499 P=0.492 P=0.226 | | |LOGISTIC REGRESSION| P=0.191 P=0.527 P=0.502 P=0.240 | | |COCH-ARM / FISHERS | P=0.194 P=0.500 P=0.500 P=0.247 | | |ORDER RESTRICTED | P=0.111 (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 10/50 (20%) 10/50 (20%) 11/50 (22%) | | |POLY-3 RATE (b) | 4/46.96 10/46.77 10/44.49 11/46.33 | | |POLY-3 PERCENT (g) | 8.5% 21.4% 22.5% 23.7% | | |TERMINAL (d) | 2/35 (6%) 8/40 (20%) 10/36 (28%) 5/35 (14%) | | |FIRST INCIDENCE | 572 605 729 (T) 491 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.098 P=0.108 P=0.079 P=0.050 | | |POLY 3 | P=0.110 P=0.071 P=0.057 P=0.041 * | | |POLY 1.5 | P=0.111 P=0.072 P=0.063 P=0.041 * | | |POLY 6 | P=0.113 P=0.070 P=0.052 P=0.041 * | | |LOGISTIC REGRESSION| P=0.125 P=0.074 P=0.066 P=0.061 | | |COCH-ARM / FISHERS | P=0.120 P=0.074 P=0.074 P=0.045 * | | |ORDER RESTRICTED | P=0.040 * (e) (e) (e) | | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 54 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Prostate | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 15/50 (30%) 10/50 (20%) 17/50 (34%) 19/50 (38%) | | |POLY-3 RATE (b) | 15/47.57 10/47.35 17/46.93 19/45.64 | | |POLY-3 PERCENT (g) | 31.5% 21.1% 36.2% 41.6% | | |TERMINAL (d) | 9/35 (26%) 7/40 (18%) 12/36 (33%) 14/35 (40%) | | |FIRST INCIDENCE | 572 548 392 562 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.069 P=0.142N P=0.430 P=0.258 | | |POLY 3 | P=0.059 P=0.179N P=0.396 P=0.212 | | |POLY 1.5 | P=0.066 P=0.177N P=0.407 P=0.228 | | |POLY 6 | P=0.054 P=0.180N P=0.382 P=0.200 | | |LOGISTIC REGRESSION| P=0.093 P=0.177N P=0.443 P=0.243 | | |COCH-ARM / FISHERS | P=0.085 P=0.178N P=0.415 P=0.263 | | |ORDER RESTRICTED | P=0.085 (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Prostate: Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 0/50 (0%) 5/50 (10%) | | |POLY-3 RATE (b) | 4/46.13 2/45.93 0/44.49 5/44.78 | | |POLY-3 PERCENT (g) | 8.7% 4.4% 0.0% 11.2% | | |TERMINAL (d) | 4/35 (11%) 2/40 (5%) 0/36 (0%) 3/35 (9%) | | |FIRST INCIDENCE | 729 (T) 729 (T) --- 598 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.206 P=0.277N P=0.059N P=0.489 | | |POLY 3 | P=0.222 P=0.339N P=0.065N P=0.482 | | |POLY 1.5 | P=0.223 P=0.338N P=0.063N P=0.486 | | |POLY 6 | P=0.221 P=0.339N P=0.066N P=0.481 | | |LOGISTIC REGRESSION| P=0.219 P=0.277N (e) P=0.492 | | |COCH-ARM / FISHERS | P=0.231 P=0.339N P=0.059N P=0.500 | | |ORDER RESTRICTED | P=0.134 (e) (e) (e) | | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 55 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Salivary Glands: Duct | | Mineralization Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 0/43.91 |0/46.00 0/44.59 0/40.77 2/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 4.2% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 2/42 (5%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.054 (e) (e) P=0.249 | |POLY 3 | (e) (e) (e) (e) |P=0.046 * (e) (e) P=0.247 | |POLY 1.5 | (e) (e) (e) (e) |P=0.045 * (e) (e) P=0.243 | |POLY 6 | (e) (e) (e) (e) |P=0.047 * (e) (e) P=0.252 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) P=0.249 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.045 * (e) (e) P=0.247 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.033 * (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Skin | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 4/50 (8%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 1/43.91 |0/46.00 0/44.99 0/40.77 4/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.3% |0.0% 0.0% 0.0% 8.3% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 1/35 (3%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 4/42 (10%) | |FIRST INCIDENCE | --- --- --- 729 (T) |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.205 (e) (e) P=0.500 |P=0.005 ** (e) (e) P=0.070 | |POLY 3 | P=0.207 (e) (e) P=0.490 |P=0.003 ** (e) (e) P=0.066 | |POLY 1.5 | P=0.209 (e) (e) P=0.493 |P=0.003 ** (e) (e) P=0.064 | |POLY 6 | P=0.205 (e) (e) P=0.487 |P=0.003 ** (e) (e) P=0.069 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.500 |(e) (e) (e) P=0.070 | |COCH-ARM / FISHERS | P=0.214 (e) (e) P=0.500 |P=0.003 ** (e) (e) P=0.059 | |ORDER RESTRICTED | P=0.111 (e) (e) (e) |P=0.002 ** (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 56 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Fibrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 0/49 (0%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 1/49 (2%) 1/48 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 2/45.45 0/45.35 2/44.72 1/44.36 |0/46.00 1/44.59 1/39.85 0/48.02 | |POLY-3 PERCENT (g) | 4.4% 0.0% 4.5% 2.3% |0.0% 2.2% 2.5% 0.0% | |TERMINAL (d) | 1/35 (3%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 1/39 (3%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 643 --- 696 598 |--- 729 (T) 641 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.619N P=0.230N P=0.688 P=0.521N |P=0.560N P=0.495 P=0.465 (e) | |POLY 3 | P=0.603N P=0.238N P=0.688 P=0.509N |P=0.564N P=0.494 P=0.471 (e) | |POLY 1.5 | P=0.599N P=0.237N P=0.693 P=0.503N |P=0.568N P=0.495 P=0.479 (e) | |POLY 6 | P=0.607N P=0.237N P=0.686 P=0.513N |P=0.559N P=0.494 P=0.462 (e) | |LOGISTIC REGRESSION| P=0.561N P=0.241N P=0.684N P=0.460N |P=0.579N P=0.495 P=0.527 (e) | |COCH-ARM / FISHERS | P=0.588N P=0.247N P=0.684N P=0.492N |P=0.574N P=0.495 P=0.490 (e) | |ORDER RESTRICTED | P=0.422N (e) (e) (e) |P=0.374N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/49 (8%) 4/49 (8%) 1/50 (2%) 6/50 (12%) |6/50 (12%) 8/49 (16%) 5/48 (10%) 4/50 (8%) | |POLY-3 RATE (b) | 4/46.06 4/46.84 1/44.70 6/45.07 |6/47.33 8/45.63 5/41.23 4/48.02 | |POLY-3 PERCENT (g) | 8.7% 8.5% 2.2% 13.3% |12.7% 17.5% 12.1% 8.3% | |TERMINAL (d) | 3/35 (9%) 1/40 (3%) 0/36 (0%) 3/35 (9%) |4/40 (10%) 5/39 (13%) 2/28 (7%) 4/42 (10%) | |FIRST INCIDENCE | 315 507 673 395 |328 538 332 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.223 P=0.603N P=0.181N P=0.368 |P=0.202N P=0.372 P=0.588 P=0.344N | |POLY 3 | P=0.230 P=0.634N P=0.188N P=0.356 |P=0.196N P=0.358 P=0.596N P=0.361N | |POLY 1.5 | P=0.236 P=0.639N P=0.183N P=0.363 |P=0.200N P=0.361 P=0.570N P=0.366N | |POLY 6 | P=0.224 P=0.623N P=0.189N P=0.353 |P=0.191N P=0.362 P=0.624 P=0.353N | |LOGISTIC REGRESSION| P=0.356 P=0.658N P=0.139N P=0.458 |P=0.221N P=0.387 P=0.350N P=0.444N | |COCH-ARM / FISHERS | P=0.250 P=0.643N P=0.175N P=0.383 |P=0.201N P=0.371 P=0.529N P=0.370N | |ORDER RESTRICTED | P=0.186 (e) (e) (e) |P=0.248N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 57 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 1/49 (2%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/49 (0%) 0/48 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/45.14 1/45.35 2/44.49 0/43.91 |0/46.00 0/44.59 0/39.53 0/48.02 | |POLY-3 PERCENT (g) | 0.0% 2.2% 4.5% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 1/40 (3%) 2/36 (6%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- 729 (T) 729 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.531N P=0.527 P=0.244 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.528N P=0.501 P=0.234 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.522N P=0.501 P=0.237 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.534N P=0.502 P=0.232 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.527 P=0.244 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.509N P=0.500 P=0.253 (e) |(e) (e) (e) (e) | |ORDER RESTRICTED | P=0.322 (e) (e) (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Spleen | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/49 (0%) 2/50 (4%) 3/50 (6%) |3/50 (6%) 2/49 (4%) 4/48 (8%) 27/50 (54%) | |POLY-3 RATE (b) | 0/45.14 0/45.35 2/44.49 3/43.91 |3/46.00 2/44.59 4/40.29 27/48.54 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.5% 6.8% |6.5% 4.5% 9.9% 55.6% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 2/36 (6%) 3/35 (9%) |3/40 (8%) 2/39 (5%) 1/28 (4%) 24/42 (57%) | |FIRST INCIDENCE | --- --- 729 (T) 729 (T) |729 (T) 729 (T) 638 638 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.031 * (e) P=0.244 P=0.121 |P<0.001 ** P=0.512N P=0.351 P<0.001 ** | |POLY 3 | P=0.033 * (e) P=0.234 P=0.114 |P<0.001 ** P=0.514N P=0.428 P<0.001 ** | |POLY 1.5 | P=0.034 * (e) P=0.237 P=0.117 |P<0.001 ** P=0.512N P=0.446 P<0.001 ** | |POLY 6 | P=0.031 * (e) P=0.232 P=0.111 |P<0.001 ** P=0.514N P=0.409 P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) P=0.244 P=0.121 |P<0.001 ** P=0.512N P=0.445 P<0.001 ** | |COCH-ARM / FISHERS | P=0.038 * (e) P=0.253 P=0.125 |P<0.001 ** P=0.510N P=0.477 P<0.001 ** | |ORDER RESTRICTED | P=0.034 * (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 58 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Diverticulum | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 1/49 (2%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 1/46.13 1/45.93 2/44.49 1/42.91 |1/46.00 1/44.99 0/40.77 2/48.02 | |POLY-3 PERCENT (g) | 2.2% 2.2% 4.5% 2.3% |2.2% 2.2% 0.0% 4.2% | |TERMINAL (d) | 1/35 (3%) 1/40 (3%) 2/36 (6%) 1/34 (3%) |1/40 (3%) 1/39 (3%) 0/28 (0%) 2/42 (5%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |729 (T) 729 (T) --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.635 P=0.732N P=0.510 P=0.755 |P=0.381 P=0.756 P=0.571N P=0.517 | |POLY 3 | P=0.632 P=0.760 P=0.487 P=0.744 |P=0.376 P=0.756 P=0.524N P=0.515 | |POLY 1.5 | P=0.639 P=0.760 P=0.492 P=0.748 |P=0.373 P=0.757 P=0.515N P=0.509 | |POLY 6 | P=0.625 P=0.760 P=0.485 P=0.741 |P=0.381 P=0.755 P=0.536N P=0.522 | |LOGISTIC REGRESSION| P=0.635 P=0.732N P=0.510 P=0.755 |P=0.381 P=0.756 (e) P=0.517 | |COCH-ARM / FISHERS | P=0.648N P=0.753N P=0.500 P=0.747 |P=0.369 P=0.753N P=0.500N P=0.500 | |ORDER RESTRICTED | P=0.563 (e) (e) (e) |P=0.297 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 1/50 (2%) 1/50 (2%) 4/49 (8%) |0/50 (0%) 2/50 (4%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 2/46.42 1/46.07 1/44.54 4/44.34 |0/46.00 2/45.29 1/41.38 1/48.18 | |POLY-3 PERCENT (g) | 4.3% 2.2% 2.3% 9.0% |0.0% 4.4% 2.4% 2.1% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 1/34 (3%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 689 693 717 395 |--- 680 532 689 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.114 P=0.506N P=0.508N P=0.320 |P=0.544 P=0.240 P=0.487 P=0.523 | |POLY 3 | P=0.116 P=0.503N P=0.514N P=0.316 |P=0.546 P=0.234 P=0.479 P=0.509 | |POLY 1.5 | P=0.118 P=0.501N P=0.509N P=0.320 |P=0.538 P=0.235 P=0.487 P=0.506 | |POLY 6 | P=0.115 P=0.504N P=0.519N P=0.313 |P=0.557 P=0.234 P=0.469 P=0.514 | |LOGISTIC REGRESSION| P=0.160 P=0.502N P=0.501N P=0.397 |P=0.507 P=0.240 P=0.611 P=0.485 | |COCH-ARM / FISHERS | P=0.121 P=0.500N P=0.500N P=0.329 |P=0.527 P=0.247 P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.121 (e) (e) (e) |P=0.254 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 59 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 0/50 (0%) 6/49 (12%) |3/50 (6%) 1/50 (2%) 4/50 (8%) 1/50 (2%) | |POLY-3 RATE (b) | 2/46.61 3/46.27 0/44.49 6/44.34 |3/46.71 1/45.18 4/42.96 1/48.02 | |POLY-3 PERCENT (g) | 4.3% 6.5% 0.0% 13.5% |6.4% 2.2% 9.3% 2.1% | |TERMINAL (d) | 0/35 (0%) 1/40 (3%) 0/36 (0%) 2/34 (6%) |1/40 (3%) 0/39 (0%) 0/28 (0%) 1/42 (2%) | |FIRST INCIDENCE | 638 675 --- 598 |605 680 532 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.046 * P=0.502 P=0.252N P=0.123 |P=0.356N P=0.317N P=0.418 P=0.288N | |POLY 3 | P=0.045 * P=0.497 P=0.248N P=0.117 |P=0.345N P=0.317N P=0.454 P=0.296N | |POLY 1.5 | P=0.046 * P=0.499 P=0.244N P=0.120 |P=0.353N P=0.313N P=0.472 P=0.299N | |POLY 6 | P=0.045 * P=0.496 P=0.251N P=0.116 |P=0.336N P=0.322N P=0.432 P=0.292N | |LOGISTIC REGRESSION| P=0.062 P=0.495 P=0.223N P=0.152 |P=0.403N P=0.292N P=0.651N P=0.342N | |COCH-ARM / FISHERS | P=0.050 P=0.500 P=0.247N P=0.128 |P=0.367N P=0.309N P=0.500 P=0.309N | |ORDER RESTRICTED | P=0.031 * (e) (e) (e) |P=0.254N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Glandular | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 1/50 (2%) 1/50 (2%) 0/49 (0%) |0/49 (0%) 1/49 (2%) 1/48 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 4/47.53 1/46.16 1/44.98 0/42.91 |0/45.49 1/44.70 1/39.61 0/48.02 | |POLY-3 PERCENT (g) | 8.4% 2.2% 2.2% 0.0% |0.0% 2.2% 2.5% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/34 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 572 668 583 --- |--- 702 710 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.082N P=0.196N P=0.206N P=0.080N |P=0.558N P=0.495 P=0.436 (e) | |POLY 3 | P=0.076N P=0.188N P=0.196N P=0.074N |P=0.564N P=0.497 P=0.472 (e) | |POLY 1.5 | P=0.075N P=0.184N P=0.189N P=0.070N |P=0.566N P=0.498 P=0.481 (e) | |POLY 6 | P=0.078N P=0.192N P=0.203N P=0.080N |P=0.560N P=0.496 P=0.462 (e) | |LOGISTIC REGRESSION| P=0.042N* P=0.192N P=0.133N P=0.041N* |P=0.567N P=0.500 P=0.471 (e) | |COCH-ARM / FISHERS | P=0.073N P=0.181N P=0.181N P=0.061N |P=0.571N P=0.500 P=0.495 (e) | |ORDER RESTRICTED | P=0.016N* (e) (e) (e) |P=0.374N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 60 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Glandular | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |1/49 (2%) 0/49 (0%) 0/48 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 2/46.77 0/45.93 0/44.49 0/42.91 |1/45.75 0/44.59 0/39.53 0/48.02 | |POLY-3 PERCENT (g) | 4.3% 0.0% 0.0% 0.0% |2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/34 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 0/42 (0%) | |FIRST INCIDENCE | 638 --- --- --- |658 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.259N P=0.252N P=0.255N P=0.268N |P=0.317N P=0.505N P=0.541N P=0.482N | |POLY 3 | P=0.242N P=0.241N P=0.249N P=0.257N |P=0.326N P=0.505N P=0.529N P=0.490N | |POLY 1.5 | P=0.243N P=0.239N P=0.244N P=0.251N |P=0.324N P=0.503N P=0.519N P=0.492N | |POLY 6 | P=0.241N P=0.243N P=0.253N P=0.263N |P=0.328N P=0.507N P=0.541N P=0.488N | |LOGISTIC REGRESSION| P=0.211N P=0.254N P=0.217N P=0.208N |P=0.319N P=0.495N P=0.479N P=0.530N | |COCH-ARM / FISHERS | P=0.245N P=0.247N P=0.247N P=0.253N |P=0.319N P=0.500N P=0.505N P=0.495N | |ORDER RESTRICTED | P=0.036N* (e) (e) (e) |P=0.111N (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Stomach, Glandular: Glands | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |0/49 (0%) 0/49 (0%) 0/48 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 1/46.18 0/45.93 0/44.49 0/42.91 |0/45.49 0/44.59 0/39.53 2/48.02 | |POLY-3 PERCENT (g) | 2.2% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 4.2% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/34 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 2/42 (5%) | |FIRST INCIDENCE | 716 --- --- --- |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.491N P=0.490N P=0.505N P=0.516N |P=0.054 (e) (e) P=0.249 | |POLY 3 | P=0.475N P=0.501N P=0.507N P=0.515N |P=0.047 * (e) (e) P=0.250 | |POLY 1.5 | P=0.476N P=0.500N P=0.505N P=0.511N |P=0.047 * (e) (e) P=0.247 | |POLY 6 | P=0.474N P=0.501N P=0.509N P=0.518N |P=0.048 * (e) (e) P=0.253 | |LOGISTIC REGRESSION| P=0.486N P=0.501N P=0.507N P=0.516N |(e) (e) (e) P=0.249 | |COCH-ARM / FISHERS | P=0.478N P=0.500N P=0.500N P=0.505N |P=0.047 * (e) (e) P=0.253 | |ORDER RESTRICTED | P=0.134N (e) (e) (e) |P=0.034 * (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 61 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Testes | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 7/50 (14%) 15/50 (30%) 13/50 (26%) | | |POLY-3 RATE (b) | 7/46.33 7/45.93 15/45.35 13/44.42 | | |POLY-3 PERCENT (g) | 15.1% 15.2% 33.1% 29.3% | | |TERMINAL (d) | 4/35 (11%) 7/40 (18%) 10/36 (28%) 9/35 (26%) | | |FIRST INCIDENCE | 694 729 (T) 644 689 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.053 P=0.523N P=0.059 P=0.108 | | |POLY 3 | P=0.049 * P=0.607 P=0.036 * P=0.083 | | |POLY 1.5 | P=0.054 P=0.610 P=0.038 * P=0.089 | | |POLY 6 | P=0.046 * P=0.604 P=0.036 * P=0.079 | | |LOGISTIC REGRESSION| P=0.046 * P=0.603N P=0.035 * P=0.076 | | |COCH-ARM / FISHERS | P=0.070 P=0.613N P=0.045 * P=0.105 | | |ORDER RESTRICTED | P=0.046 * (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Testes: Bilateral | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 2/50 (4%) 0/50 (0%) | | |POLY-3 RATE (b) | 2/46.32 3/45.93 2/44.63 0/43.91 | | |POLY-3 PERCENT (g) | 4.3% 6.5% 4.5% 0.0% | | |TERMINAL (d) | 0/35 (0%) 3/40 (8%) 1/36 (3%) 0/35 (0%) | | |FIRST INCIDENCE | 694 729 (T) 694 --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.132N P=0.538 P=0.688 P=0.260N | | |POLY 3 | P=0.128N P=0.496 P=0.680 P=0.249N | | |POLY 1.5 | P=0.124N P=0.499 P=0.685 P=0.245N | | |POLY 6 | P=0.131N P=0.494 P=0.677 P=0.253N | | |LOGISTIC REGRESSION| P=0.126N P=0.499 P=0.688 P=0.242N | | |COCH-ARM / FISHERS | P=0.116N P=0.500 P=0.691N P=0.247N | | |ORDER RESTRICTED | P=0.143N (e) (e) (e) | | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 62 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Testes: Bilateral, Interstitial Cell | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/44.49 2/43.91 | | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.6% | | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 2/35 (6%) | | |FIRST INCIDENCE | --- --- --- 729 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.037 * (e) (e) P=0.238 | | |POLY 3 | P=0.038 * (e) (e) P=0.226 | | |POLY 1.5 | P=0.039 * (e) (e) P=0.230 | | |POLY 6 | P=0.038 * (e) (e) P=0.223 | | |LOGISTIC REGRESSION| (e) (e) (e) P=0.238 | | |COCH-ARM / FISHERS | P=0.042 * (e) (e) P=0.247 | | |ORDER RESTRICTED | P=0.026 * (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 1/50 (2%) 1/50 (2%) | | |POLY-3 RATE (b) | 2/47.08 3/46.60 1/44.49 1/44.42 | | |POLY-3 PERCENT (g) | 4.3% 6.4% 2.3% 2.3% | | |TERMINAL (d) | 0/35 (0%) 1/40 (3%) 1/36 (3%) 0/35 (0%) | | |FIRST INCIDENCE | 572 608 729 (T) 574 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.322N P=0.501 P=0.517N P=0.525N | | |POLY 3 | P=0.314N P=0.495 P=0.520N P=0.520N | | |POLY 1.5 | P=0.308N P=0.498 P=0.512N P=0.513N | | |POLY 6 | P=0.319N P=0.495 P=0.527N P=0.527N | | |LOGISTIC REGRESSION| P=0.225N P=0.465 P=0.466N P=0.405N | | |COCH-ARM / FISHERS | P=0.296N P=0.500 P=0.500N P=0.500N | | |ORDER RESTRICTED | P=0.354N (e) (e) (e) | | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 63 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Testes: Interstitial Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 1/50 (2%) 1/50 (2%) | | |POLY-3 RATE (b) | 0/46.13 2/45.93 1/44.49 1/43.91 | | |POLY-3 PERCENT (g) | 0.0% 4.4% 2.3% 2.3% | | |TERMINAL (d) | 0/35 (0%) 2/40 (5%) 1/36 (3%) 1/35 (3%) | | |FIRST INCIDENCE | --- 729 (T) 729 (T) 729 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.602 P=0.268 P=0.506 P=0.500 | | |POLY 3 | P=0.599 P=0.236 P=0.493 P=0.490 | | |POLY 1.5 | P=0.605 P=0.237 P=0.495 P=0.493 | | |POLY 6 | P=0.594 P=0.236 P=0.491 P=0.487 | | |LOGISTIC REGRESSION| (e) P=0.268 P=0.506 P=0.500 | | |COCH-ARM / FISHERS | P=0.619 P=0.247 P=0.500 P=0.500 | | |ORDER RESTRICTED | P=0.271 (e) (e) (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Testes: Interstitial Cell | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 4/50 (8%) 4/50 (8%) 11/50 (22%) | | |POLY-3 RATE (b) | 1/46.26 4/46.93 4/44.98 11/44.51 | | |POLY-3 PERCENT (g) | 2.2% 8.5% 8.9% 24.7% | | |TERMINAL (d) | 0/35 (0%) 2/40 (5%) 3/36 (8%) 9/35 (26%) | | |FIRST INCIDENCE | 694 548 583 598 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.197 P=0.183 P=0.003 ** | | |POLY 3 | P<0.001 ** P=0.183 P=0.170 P<0.001 ** | | |POLY 1.5 | P<0.001 ** P=0.182 P=0.173 P=0.002 ** | | |POLY 6 | P<0.001 ** P=0.186 P=0.168 P<0.001 ** | | |LOGISTIC REGRESSION| P<0.001 ** P=0.163 P=0.182 P=0.002 ** | | |COCH-ARM / FISHERS | P<0.001 ** P=0.181 P=0.181 P=0.002 ** | | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 64 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Thymus | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/48 (0%) 0/44 (0%) 0/49 (0%) |0/48 (0%) 0/45 (0%) 2/49 (4%) 0/49 (0%) | |POLY-3 RATE (b) | 0/44.39 0/43.93 0/40.49 0/43.06 |0/44.00 0/41.15 2/40.53 0/47.15 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 4.9% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/38 (0%) 0/33 (0%) 0/35 (0%) |0/38 (0%) 0/37 (0%) 0/27 (0%) 0/42 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- --- 548 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.584 (e) P=0.207 (e) | |POLY 3 | (e) (e) (e) (e) |P=0.620 (e) P=0.219 (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.607 (e) P=0.228 (e) | |POLY 6 | (e) (e) (e) (e) |P=0.634 (e) P=0.209 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.569 (e) P=0.294 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.585 (e) P=0.253 (e) | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.233 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Thymus | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/48 (4%) 1/48 (2%) 1/44 (2%) 0/49 (0%) |1/48 (2%) 1/45 (2%) 0/49 (0%) 2/49 (4%) | |POLY-3 RATE (b) | 2/44.39 1/43.93 1/40.49 0/43.06 |1/44.43 1/41.86 0/39.77 2/47.15 | |POLY-3 PERCENT (g) | 4.5% 2.3% 2.5% 0.0% |2.3% 2.4% 0.0% 4.2% | |TERMINAL (d) | 2/35 (6%) 1/38 (3%) 1/33 (3%) 0/35 (0%) |0/38 (0%) 0/37 (0%) 0/27 (0%) 2/42 (5%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) --- |602 483 --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.201N P=0.471N P=0.521N P=0.238N |P=0.389 P=0.753 P=0.532N P=0.528 | |POLY 3 | P=0.201N P=0.504N P=0.532N P=0.244N |P=0.387 P=0.747 P=0.522N P=0.521 | |POLY 1.5 | P=0.199N P=0.501N P=0.531N P=0.240N |P=0.386 P=0.747 P=0.512N P=0.515 | |POLY 6 | P=0.203N P=0.506N P=0.533N P=0.247N |P=0.390 P=0.749 P=0.535N P=0.527 | |LOGISTIC REGRESSION| P=0.201N P=0.471N P=0.521N (e) |P=0.350 P=0.757 P=0.434N P=0.476 | |COCH-ARM / FISHERS | P=0.192N P=0.500N P=0.533N P=0.242N |P=0.383 P=0.736 P=0.495N P=0.508 | |ORDER RESTRICTED | P=0.123N (e) (e) (e) |P=0.306 (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 65 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 41/48 (85%) 43/46 (93%) 38/43 (88%) 34/50 (68%) |48/49 (98%) 46/48 (96%) 40/42 (95%) 25/48 (52%) | |POLY-3 RATE (b) | 41/47.64 43/45.63 38/42.68 34/47.78 |48/48.51 46/47.09 40/41.05 25/47.36 | |POLY-3 PERCENT (g) | 86.1% 94.2% 89.0% 71.2% |99.0% 97.7% 97.5% 52.8% | |TERMINAL (d) | 30/35 (86%) 38/39 (97%) 32/35 (91%) 24/35 (69%) |40/40 (100%) 39/39 (100%) 28/28 (100%) 22/41 (54%) | |FIRST INCIDENCE | 572 507 471 491 |328 483 244 644 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.104N P=0.455N P=0.373N P=0.182N |P<0.001N** P=0.519N P=0.150 P<0.001N** | |POLY 3 | P=0.003N** P=0.158 P=0.457 P=0.059N |P<0.001N** P=0.647N P=0.641N P<0.001N** | |POLY 1.5 | P=0.002N** P=0.167 P=0.458 P=0.052N |P<0.001N** P=0.592N P=0.535N P<0.001N** | |POLY 6 | P=0.002N** P=0.145 P=0.456 P=0.061N |P<0.001N** P=0.686N P=0.864N P<0.001N** | |LOGISTIC REGRESSION| P=0.002N** P=0.176 P=0.460 P=0.050N |P<0.001N** P=0.502N P=0.573N P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P=0.176 P=0.460 P=0.035N* |P<0.001N** P=0.492N P=0.442N P<0.001N** | |ORDER RESTRICTED | P=0.004N** (e) (e) (e) |P<0.001N** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicle | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/48 (2%) 0/46 (0%) 0/43 (0%) 1/50 (2%) |0/49 (0%) 2/48 (4%) 1/42 (2%) 0/48 (0%) | |POLY-3 RATE (b) | 1/45.21 0/43.50 0/40.29 1/43.91 |0/45.28 2/43.78 1/35.80 0/46.81 | |POLY-3 PERCENT (g) | 2.2% 0.0% 0.0% 2.3% |0.0% 4.6% 2.8% 0.0% | |TERMINAL (d) | 0/35 (0%) 0/39 (0%) 0/35 (0%) 1/35 (3%) |0/40 (0%) 2/39 (5%) 0/28 (0%) 0/41 (0%) | |FIRST INCIDENCE | 689 --- --- 729 (T) |--- 729 (T) 668 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.527 P=0.505N P=0.510N P=0.755 |P=0.420N P=0.233 P=0.458 (e) | |POLY 3 | P=0.534 P=0.508N P=0.523N P=0.754 |P=0.418N P=0.230 P=0.453 (e) | |POLY 1.5 | P=0.539 P=0.508N P=0.523N P=0.759 |P=0.424N P=0.231 P=0.459 (e) | |POLY 6 | P=0.528 P=0.506N P=0.521N P=0.750 |P=0.412N P=0.229 P=0.448 (e) | |LOGISTIC REGRESSION| P=0.545 P=0.499N P=0.507N P=0.763 |P=0.427N P=0.233 P=0.485 (e) | |COCH-ARM / FISHERS | P=0.550 P=0.511N P=0.527N P=0.742N |P=0.433N P=0.242 P=0.462 (e) | |ORDER RESTRICTED | P=0.399 (e) (e) (e) |P=0.287N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 66 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicle | | Mineralization Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 48/48 (100%) 45/46 (98%) 43/43 (100%) 49/50 (98%) |42/49 (86%) 47/48 (98%) 41/42 (98%) 48/48 (100%) | |POLY-3 RATE (b) | 48/48.00 45/45.77 43/43.00 49/49.31 |42/46.64 47/47.20 41/41.04 48/48.00 | |POLY-3 PERCENT (g) | 100.0% 98.3% 100.0% 99.4% |90.1% 99.6% 99.9% 100.0% | |TERMINAL (d) | 35/35 (100%) 39/39 (100%) 35/35 (100%) 35/35 (100%)|38/40 (95%) 39/39 (100%) 28/28 (100%) 41/41 (100%) | |FIRST INCIDENCE | 572 507 471 249 |602 483 332 638 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.146 P=0.089N (e) P=0.435 |P=0.211 P=0.085 P=0.005 ** P=0.163 | |POLY 3 | P=0.833 P=0.608N (e) P=0.988N |P=0.007 ** P=0.031 * P=0.036 * P=0.022 * | |POLY 1.5 | P=0.700N P=0.547N (e) P=0.794N |P=0.004 ** P=0.028 * P=0.030 * P=0.014 * | |POLY 6 | P=0.835 P=0.746N (e) P=1.000N |P=0.018 * P=0.048 * P=0.062 P=0.043 * | |LOGISTIC REGRESSION| P=0.723N P=0.522N (e) P=0.771N |P=0.003 ** P=0.008 ** P=0.006 ** P=0.063 | |COCH-ARM / FISHERS | P=0.479N P=0.489N (e) P=0.510N |P=0.006 ** P=0.032 * P=0.048 * P=0.007 ** | |ORDER RESTRICTED | P=0.411N (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 17/46 (37%) 37/43 (86%) 43/50 (86%) |0/49 (0%) 41/48 (85%) 34/42 (81%) 46/48 (96%) | |POLY-3 RATE (b) | 0/45.06 17/43.50 37/41.51 43/49.31 |0/45.28 41/46.66 34/38.28 46/47.79 | |POLY-3 PERCENT (g) | 0.0% 39.1% 89.1% 87.2% |0.0% 87.9% 88.8% 96.3% | |TERMINAL (d) | 0/35 (0%) 17/39 (44%) 33/35 (94%) 31/35 (89%) |0/40 (0%) 36/39 (92%) 27/28 (96%) 40/41 (98%) | |FIRST INCIDENCE | --- 729 (T) 538 249 |--- 425 332 638 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) |P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 67 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Urinary Bladder: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) |0/50 (0%) 0/49 (0%) 0/49 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/46.13 0/45.93 0/43.72 0/43.91 |0/46.00 0/44.59 0/40.34 2/48.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 4.2% | |TERMINAL (d) | 0/35 (0%) 0/40 (0%) 0/36 (0%) 0/35 (0%) |0/40 (0%) 0/39 (0%) 0/28 (0%) 2/42 (5%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.054 (e) (e) P=0.249 | |POLY 3 | (e) (e) (e) (e) |P=0.046 * (e) (e) P=0.247 | |POLY 1.5 | (e) (e) (e) (e) |P=0.046 * (e) (e) P=0.243 | |POLY 6 | (e) (e) (e) (e) |P=0.047 * (e) (e) P=0.252 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) P=0.249 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.046 * (e) (e) P=0.247 | |ORDER RESTRICTED | (e) (e) (e) (e) |P=0.033 * (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Uterus | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |3/50 (6%) 0/50 (0%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | |3/46.42 0/44.99 1/41.10 1/48.02 | |POLY-3 PERCENT (g) | |6.5% 0.0% 2.4% 2.1% | |TERMINAL (d) | |2/40 (5%) 0/39 (0%) 0/28 (0%) 1/42 (2%) | |FIRST INCIDENCE | |605 --- 638 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.320N P=0.129N P=0.397N P=0.289N | |POLY 3 | |P=0.318N P=0.124N P=0.350N P=0.293N | |POLY 1.5 | |P=0.322N P=0.122N P=0.332N P=0.298N | |POLY 6 | |P=0.314N P=0.126N P=0.373N P=0.288N | |LOGISTIC REGRESSION| |P=0.329N P=0.118N P=0.285N P=0.319N | |COCH-ARM / FISHERS | |P=0.326N P=0.121N P=0.309N P=0.309N | |ORDER RESTRICTED | |P=0.100N (e) (e) (e) | |=================================================================================================================================| Date: 03/14/03 EXPERIMENT: 92012 TEST: 05 Page 68 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - 2-METHYLIMIDAZOLE Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Uterus | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |POLY-3 RATE (b) | |0/46.00 0/44.99 2/40.77 0/48.02 | |POLY-3 PERCENT (g) | |0.0% 0.0% 4.9% 0.0% | |TERMINAL (d) | |0/40 (0%) 0/39 (0%) 2/28 (7%) 0/42 (0%) | |FIRST INCIDENCE | |--- --- 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.576 (e) P=0.164 (e) | |POLY 3 | |P=0.613 (e) P=0.211 (e) | |POLY 1.5 | |P=0.599 (e) P=0.221 (e) | |POLY 6 | |P=0.628 (e) P=0.199 (e) | |LOGISTIC REGRESSION| |(e) (e) P=0.164 (e) | |COCH-ARM / FISHERS | |P=0.575 (e) P=0.247 (e) | |ORDER RESTRICTED | |P=0.223 (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0PPM 300 PPM 1000 PPM 3000 PPM |0PPM 1000 PPM 2500 PPM 5000 PPM | | | | | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |10/50 (20%) 14/50 (28%) 15/50 (30%) 15/50 (30%) | |POLY-3 RATE (b) | |10/46.22 14/45.70 15/40.77 15/48.66 | |POLY-3 PERCENT (g) | |21.6% 30.6% 36.8% 30.8% | |TERMINAL (d) | |9/40 (23%) 13/39 (33%) 15/28 (54%) 13/42 (31%) | |FIRST INCIDENCE | |671 483 729 (T) 638 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.215 P=0.220 P=0.019 * P=0.225 | |POLY 3 | |P=0.231 P=0.228 P=0.091 P=0.217 | |POLY 1.5 | |P=0.211 P=0.234 P=0.121 P=0.201 | |POLY 6 | |P=0.261 P=0.223 P=0.060 P=0.240 | |LOGISTIC REGRESSION| |P=0.244 P=0.220 P=0.031 * P=0.210 | |COCH-ARM / FISHERS | |P=0.187 P=0.241 P=0.178 P=0.178 | |ORDER RESTRICTED | |P=0.148 (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).