TDMS Study 05211-05 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Southern Research Inst EMODIN DATE: 01/25/01 EXPERIMENT: 05211 TEST: 05 TIME: 13:06:07 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-85216 ROUTE: DOSED FEED NTP C#: C62408 PATHOLOGIST: HEATH, JAMES CAS: 518-82-1 ------------------------------------------------------------------------------------------------------------------------------------ FINAL#3;REVISION#1 REASONS FOR REMOVAL: 25022 Accidently Killed 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 EMODIN DATE: 01/25/01 EXPERIMENT: 05211 TEST: 05 TIME: 13:06:07 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-85216 ROUTE: DOSED FEED NTP C#: C62408 PATHOLOGIST: HEATH, JAMES CAS: 518-82-1 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF EMODIN =============================================================== Male Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Accessory Adrenal Cortical Nodule Adrenal Medulla Hyperplasia Bone Marrow Hyperplasia Heart Thrombosis Intestine Large, Cecum Inflammation Chronic Intestine Large, Cecum: Epithelium Hyperplasia Islets, Pancreatic Hyperplasia Kidney Hydronephrosis Infarct Inflammation Chronic Nephropathy Kidney: Renal Tubule Hyaline Droplet Pigmentation Liver Angiectasis Liver: Bile Duct Hyperplasia Lung Infiltration Cellular Histiocyte Lymph Node, Mesenteric Ectasia Mammary Gland Hyperplasia Mesentery Accessory Spleen Pituitary Gland: Pars Distalis Hyperplasia Focal Prostate: Epithelium Hyperplasia Spleen Fibrosis =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Atrophy Brain Hydrocephalus Kidney Infarct Kidney: Renal Tubule Hyaline Droplet Hyperplasia Oncocytic Liver Angiectasis Clear Cell Focus Eosinophilic Focus Necrosis Focal Lymph Node, Mandibular Ectasia Pigmentation Nose: Respiratory Epithelium Hyperplasia Pituitary Gland: Pars Distalis Cyst Hyperplasia Focal Spleen Fibrosis Hematopoietic Cell Proliferation Pigmentation Thyroid Gland: C-Cell Hyperplasia Uterus Hyperplasia Cystic =============================================================== Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Accessory Adrenal Cortical Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 13/50 (26%) 18/50 (36%) 16/50 (32%) 10/50 (20%) |6/49 (12%) 4/50 (8%) 7/50 (14%) 10/50 (20%) | |POLY-3 RATE (b) | 13/42.15 18/41.41 16/41.38 10/43.75 |6/44.80 4/46.19 7/46.17 10/44.85 | |POLY-3 PERCENT (g) | 30.8% 43.5% 38.7% 22.9% |13.4% 8.7% 15.2% 22.3% | |TERMINAL (d) | 10/30 (33%) 11/21 (52%) 9/21 (43%) 4/30 (13%) |3/33 (9%) 3/39 (8%) 5/35 (14%) 8/34 (24%) | |FIRST INCIDENCE | 590 511 617 590 |610 600 527 602 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.070N P=0.041 * P=0.108 P=0.315N |P=0.066 P=0.305N P=0.541 P=0.219 | |POLY 3 | P=0.076N P=0.161 P=0.299 P=0.276N |P=0.069 P=0.350N P=0.523 P=0.204 | |POLY 1.5 | P=0.088N P=0.192 P=0.330 P=0.280N |P=0.073 P=0.354N P=0.517 P=0.210 | |POLY 6 | P=0.064N P=0.115 P=0.249 P=0.278N |P=0.064 P=0.344N P=0.532 P=0.197 | |LOGISTIC REGRESSION| P=0.083N P=0.146 P=0.278 P=0.285N |P=0.080 P=0.360N P=0.519 P=0.214 | |COCH-ARM / FISHERS | P=0.119N P=0.194 P=0.330 P=0.318N |P=0.079 P=0.357N P=0.516 P=0.220 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/40.89 0/39.45 0/39.45 0/42.44 |0/44.01 0/45.74 0/45.30 2/44.48 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 4.5% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 0/30 (0%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 1/34 (3%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 592 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.041 * (e) (e) P=0.245 | |POLY 3 | (e) (e) (e) (e) |P=0.041 * (e) (e) P=0.239 | |POLY 1.5 | (e) (e) (e) (e) |P=0.041 * (e) (e) P=0.240 | |POLY 6 | (e) (e) (e) (e) |P=0.040 * (e) (e) P=0.239 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.045 * (e) (e) P=0.257 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.042 * (e) (e) P=0.253 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Degeneration Fatty | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 9/50 (18%) 10/50 (20%) 8/50 (16%) |12/49 (24%) 9/50 (18%) 14/50 (28%) 10/50 (20%) | |POLY-3 RATE (b) | 7/41.44 9/41.31 10/40.09 8/42.44 |12/44.43 9/45.90 14/45.34 10/45.01 | |POLY-3 PERCENT (g) | 16.9% 21.8% 25.0% 18.9% |27.0% 19.6% 30.9% 22.2% | |TERMINAL (d) | 5/30 (17%) 2/21 (10%) 6/21 (29%) 8/30 (27%) |9/33 (27%) 8/39 (21%) 12/35 (34%) 7/34 (21%) | |FIRST INCIDENCE | 599 506 644 729 (T) |648 690 725 603 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.449N P=0.230 P=0.118 P=0.504 |P=0.509N P=0.193N P=0.480 P=0.391N | |POLY 3 | P=0.547N P=0.388 P=0.266 P=0.520 |P=0.458N P=0.280N P=0.432 P=0.390N | |POLY 1.5 | P=0.550N P=0.406 P=0.293 P=0.524 |P=0.452N P=0.287N P=0.427 P=0.389N | |POLY 6 | P=0.551N P=0.354 P=0.221 P=0.506 |P=0.465N P=0.268N P=0.439 P=0.389N | |LOGISTIC REGRESSION| P=0.507N P=0.382 P=0.216 P=0.520 |P=0.499N P=0.251N P=0.474 P=0.406N | |COCH-ARM / FISHERS | P=0.554 P=0.393 P=0.298 P=0.500 |P=0.442N P=0.294N P=0.433 P=0.384N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 1/50 (2%) 1/50 (2%) |1/49 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/40.89 2/39.60 1/39.86 1/42.86 |1/44.11 0/45.74 0/45.30 0/44.02 | |POLY-3 PERCENT (g) | 0.0% 5.1% 2.5% 2.3% |2.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 1/21 (5%) 0/21 (0%) 0/30 (0%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 690 609 607 |704 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.638 P=0.178 P=0.505 P=0.515 |P=0.486N P=0.484N P=0.495N P=0.511N | |POLY 3 | P=0.633 P=0.230 P=0.495 P=0.509 |P=0.472N P=0.493N P=0.495N P=0.500N | |POLY 1.5 | P=0.630 P=0.237 P=0.501 P=0.508 |P=0.471N P=0.494N P=0.496N P=0.499N | |POLY 6 | P=0.633 P=0.216 P=0.484 P=0.509 |P=0.474N P=0.490N P=0.492N P=0.503N | |LOGISTIC REGRESSION| P=0.610 P=0.211 P=0.487 P=0.474 |P=0.472N P=0.495N P=0.496N P=0.498N | |COCH-ARM / FISHERS | P=0.614 P=0.247 P=0.500 P=0.500 |P=0.470N P=0.495N P=0.495N P=0.495N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 4/50 (8%) 2/50 (4%) |3/49 (6%) 3/50 (6%) 8/50 (16%) 7/50 (14%) | |POLY-3 RATE (b) | 3/40.99 0/39.45 4/39.88 2/42.44 |3/44.03 3/46.09 8/46.01 7/44.65 | |POLY-3 PERCENT (g) | 7.3% 0.0% 10.0% 4.7% |6.8% 6.5% 17.4% 15.7% | |TERMINAL (d) | 2/30 (7%) 0/21 (0%) 3/21 (14%) 2/30 (7%) |2/33 (6%) 2/39 (5%) 3/35 (9%) 5/34 (15%) | |FIRST INCIDENCE | 704 --- 605 729 (T) |725 634 665 610 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.570N P=0.184N P=0.347 P=0.500N |P=0.095 P=0.597N P=0.132 P=0.168 | |POLY 3 | P=0.610N P=0.125N P=0.485 P=0.484N |P=0.103 P=0.641N P=0.112 P=0.162 | |POLY 1.5 | P=0.610 P=0.119N P=0.501 P=0.484N |P=0.106 P=0.647N P=0.107 P=0.163 | |POLY 6 | P=0.591N P=0.138N P=0.454 P=0.489N |P=0.098 P=0.631N P=0.121 P=0.162 | |LOGISTIC REGRESSION| P=0.600N P=0.153N P=0.450 P=0.494N |P=0.105 P=0.646N P=0.109 P=0.157 | |COCH-ARM / FISHERS | P=0.589 P=0.121N P=0.500 P=0.500N |P=0.113 P=0.651N P=0.106 P=0.167 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 9/50 (18%) 7/50 (14%) 3/50 (6%) |12/49 (24%) 7/50 (14%) 12/50 (24%) 10/50 (20%) | |POLY-3 RATE (b) | 6/41.79 9/41.88 7/41.33 3/42.44 |12/45.06 7/46.42 12/45.46 10/44.94 | |POLY-3 PERCENT (g) | 14.4% 21.5% 16.9% 7.1% |26.6% 15.1% 26.4% 22.3% | |TERMINAL (d) | 4/30 (13%) 2/21 (10%) 2/21 (10%) 3/30 (10%) |9/33 (27%) 5/39 (13%) 9/35 (26%) 8/34 (24%) | |FIRST INCIDENCE | 597 506 483 729 (T) |544 572 702 529 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.079N P=0.184 P=0.369 P=0.236N |P=0.517 P=0.095N P=0.533N P=0.386N | |POLY 3 | P=0.086N P=0.285 P=0.491 P=0.233N |P=0.547 P=0.134N P=0.584N P=0.406N | |POLY 1.5 | P=0.087N P=0.300 P=0.508 P=0.230N |P=0.560N P=0.138N P=0.583N P=0.398N | |POLY 6 | P=0.088N P=0.258 P=0.458 P=0.242N |P=0.527 P=0.126N P=0.582N P=0.417N | |LOGISTIC REGRESSION| P=0.096N P=0.288 P=0.501 P=0.226N |P=0.556 P=0.141N P=0.556N P=0.393N | |COCH-ARM / FISHERS | P=0.097N P=0.288 P=0.500 P=0.243N |P=0.541N P=0.142N P=0.570N P=0.384N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Cortex | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/49 (0%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/40.89 1/40.11 0/39.45 0/42.44 |0/44.01 2/46.62 0/45.30 0/44.02 | |POLY-3 PERCENT (g) | 0.0% 2.5% 0.0% 0.0% |0.0% 4.3% 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 0/30 (0%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 506 --- --- |--- 600 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.583N P=0.509 (e) (e) |P=0.389N P=0.247 (e) (e) | |POLY 3 | P=0.586N P=0.496 (e) (e) |P=0.376N P=0.250 (e) (e) | |POLY 1.5 | P=0.583N P=0.502 (e) (e) |P=0.378N P=0.246 (e) (e) | |POLY 6 | P=0.591N P=0.485 (e) (e) |P=0.373N P=0.257 (e) (e) | |LOGISTIC REGRESSION| P=0.654N P=0.407 (e) (e) |P=0.350N P=0.257 (e) (e) | |COCH-ARM / FISHERS | P=0.587N P=0.500 (e) (e) |P=0.379N P=0.253 (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 9/49 (18%) 7/50 (14%) 17/50 (34%) |2/47 (4%) 2/50 (4%) 2/50 (4%) 3/50 (6%) | |POLY-3 RATE (b) | 10/41.49 9/39.51 7/40.01 17/43.51 |2/42.97 2/45.74 2/45.30 3/44.02 | |POLY-3 PERCENT (g) | 24.1% 22.8% 17.5% 39.1% |4.7% 4.4% 4.4% 6.8% | |TERMINAL (d) | 6/30 (20%) 4/20 (20%) 4/21 (19%) 11/30 (37%) |1/33 (3%) 2/39 (5%) 2/35 (6%) 3/34 (9%) | |FIRST INCIDENCE | 617 596 638 605 |686 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.081 P=0.415 P=0.549N P=0.108 |P=0.372 P=0.641N P=0.675N P=0.508 | |POLY 3 | P=0.030 * P=0.549N P=0.322N P=0.102 |P=0.393 P=0.671N P=0.675N P=0.511 | |POLY 1.5 | P=0.028 * P=0.517N P=0.297N P=0.102 |P=0.401 P=0.672N P=0.675N P=0.518 | |POLY 6 | P=0.034 * P=0.605 P=0.371N P=0.099 |P=0.382 P=0.669N P=0.674N P=0.503 | |LOGISTIC REGRESSION| P=0.040 * P=0.602 P=0.380N P=0.097 |P=0.372 P=0.668N P=0.672N P=0.503 | |COCH-ARM / FISHERS | P=0.025 * P=0.520N P=0.298N P=0.088 |P=0.411 P=0.668N P=0.668N P=0.530 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 5/50 (10%) 3/50 (6%) 11/50 (22%) |5/49 (10%) 3/50 (6%) 4/50 (8%) 6/50 (12%) | |POLY-3 RATE (b) | 3/43.19 5/40.25 3/40.41 11/44.90 |5/44.64 3/46.58 4/46.35 6/46.26 | |POLY-3 PERCENT (g) | 7.0% 12.4% 7.4% 24.5% |11.2% 6.4% 8.6% 13.0% | |TERMINAL (d) | 0/30 (0%) 2/21 (10%) 0/21 (0%) 5/30 (17%) |2/33 (6%) 2/39 (5%) 2/35 (6%) 1/34 (3%) | |FIRST INCIDENCE | 122 610 603 590 |630 396 232 360 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.017 * P=0.292 P=0.647 P=0.033 * |P=0.283 P=0.307N P=0.475N P=0.498 | |POLY 3 | P=0.007 ** P=0.317 P=0.632 P=0.023 * |P=0.307 P=0.333N P=0.477N P=0.525 | |POLY 1.5 | P=0.007 ** P=0.340 P=0.648 P=0.022 * |P=0.307 P=0.338N P=0.481N P=0.521 | |POLY 6 | P=0.009 ** P=0.284 P=0.605 P=0.024 * |P=0.306 P=0.328N P=0.473N P=0.528 | |LOGISTIC REGRESSION| P=0.003 ** P=0.253 P=0.525 P=0.009 ** |P=0.370 P=0.348N P=0.450N P=0.580 | |COCH-ARM / FISHERS | P=0.006 ** P=0.357 P=0.661N P=0.020 * |P=0.305 P=0.346N P=0.487N P=0.514 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Bone Marrow | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/49 (0%) 2/50 (4%) 4/50 (8%) 2/50 (4%) | |POLY-3 RATE (b) | 0/40.89 0/39.45 0/39.45 0/42.44 |0/44.01 2/45.74 4/45.70 2/44.18 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 4.4% 8.8% 4.5% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 0/30 (0%) |0/33 (0%) 2/39 (5%) 3/35 (9%) 1/34 (3%) | |FIRST INCIDENCE | --- --- --- --- |--- 730 (T) 617 689 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.359 P=0.276 P=0.072 P=0.243 | |POLY 3 | (e) (e) (e) (e) |P=0.370 P=0.246 P=0.065 P=0.238 | |POLY 1.5 | (e) (e) (e) (e) |P=0.376 P=0.244 P=0.064 P=0.239 | |POLY 6 | (e) (e) (e) (e) |P=0.364 P=0.249 P=0.067 P=0.237 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.373 P=0.276 P=0.065 P=0.238 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.385 P=0.253 P=0.061 P=0.253 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Bone: Cranium | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |7/49 (14%) 5/50 (10%) 6/50 (12%) 8/50 (16%) | |POLY-3 RATE (b) | 1/41.51 0/39.45 0/39.45 0/42.44 |7/45.09 5/45.74 6/46.98 8/44.17 | |POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 0.0% |15.5% 10.9% 12.8% 18.1% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 0/30 (0%) |4/33 (12%) 5/39 (13%) 2/35 (6%) 7/34 (21%) | |FIRST INCIDENCE | 528 --- --- --- |610 730 (T) 539 690 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.465N P=0.500N P=0.496N P=0.491N |P=0.297 P=0.296N P=0.463N P=0.510 | |POLY 3 | P=0.464N P=0.510N P=0.510N P=0.496N |P=0.304 P=0.369N P=0.468N P=0.483 | |POLY 1.5 | P=0.471N P=0.502N P=0.502N P=0.495N |P=0.318 P=0.368N P=0.479N P=0.497 | |POLY 6 | P=0.451N P=0.525N P=0.524N P=0.499N |P=0.287 P=0.369N P=0.455N P=0.463 | |LOGISTIC REGRESSION| P=0.524N P=0.573N P=0.558N P=0.569N |P=0.337 P=0.362N P=0.461N P=0.504 | |COCH-ARM / FISHERS | P=0.472N P=0.500N P=0.500N P=0.500N |P=0.335 P=0.365N P=0.484N P=0.517 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Bone: Femur | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |6/49 (12%) 8/50 (16%) 7/50 (14%) 7/50 (14%) | |POLY-3 RATE (b) | 0/40.89 0/39.45 0/39.45 0/42.44 |6/44.67 8/46.02 7/45.81 7/44.33 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |13.4% 17.4% 15.3% 15.8% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 0/30 (0%) |4/33 (12%) 7/39 (18%) 5/35 (14%) 5/34 (15%) | |FIRST INCIDENCE | --- --- --- --- |630 656 617 689 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.506 P=0.497 P=0.543 P=0.510 | |POLY 3 | (e) (e) (e) (e) |P=0.527 P=0.409 P=0.519 P=0.494 | |POLY 1.5 | (e) (e) (e) (e) |P=0.539 P=0.405 P=0.514 P=0.502 | |POLY 6 | (e) (e) (e) (e) |P=0.511 P=0.417 P=0.528 P=0.484 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.532 P=0.413 P=0.516 P=0.501 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.557 P=0.403 P=0.516 P=0.516 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Brain | | Compression | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 2/50 (4%) 5/50 (10%) 5/50 (10%) |8/49 (16%) 7/50 (14%) 10/50 (20%) 7/50 (14%) | |POLY-3 RATE (b) | 4/41.82 2/40.18 5/40.70 5/42.74 |8/45.84 7/46.96 10/46.31 7/45.26 | |POLY-3 PERCENT (g) | 9.6% 5.0% 12.3% 11.7% |17.5% 14.9% 21.6% 15.5% | |TERMINAL (d) | 1/30 (3%) 0/21 (0%) 1/21 (5%) 4/30 (13%) |3/33 (9%) 4/39 (10%) 6/35 (17%) 2/34 (6%) | |FIRST INCIDENCE | 604 561 483 645 |497 572 648 610 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.378 P=0.404N P=0.406 P=0.510 |P=0.515N P=0.421N P=0.458 P=0.504N | |POLY 3 | P=0.329 P=0.355N P=0.483 P=0.514 |P=0.502N P=0.480N P=0.406 P=0.511N | |POLY 1.5 | P=0.320 P=0.338N P=0.502 P=0.517 |P=0.488N P=0.483N P=0.405 P=0.501N | |POLY 6 | P=0.339 P=0.387N P=0.446 P=0.502 |P=0.518N P=0.472N P=0.413 P=0.520N | |LOGISTIC REGRESSION| P=0.304 P=0.341N P=0.499 P=0.517 |P=0.439N P=0.501N P=0.424 P=0.444N | |COCH-ARM / FISHERS | P=0.301 P=0.339N P=0.500 P=0.500 |P=0.466N P=0.483N P=0.416 P=0.483N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Brain | | Hydrocephalus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 1/50 (2%) |3/49 (6%) 0/50 (0%) 3/50 (6%) 7/50 (14%) | |POLY-3 RATE (b) | 1/41.29 1/39.45 2/40.32 1/42.44 |3/44.77 0/45.74 3/45.76 7/44.86 | |POLY-3 PERCENT (g) | 2.4% 2.5% 5.0% 2.4% |6.7% 0.0% 6.6% 15.6% | |TERMINAL (d) | 0/30 (0%) 1/21 (5%) 1/21 (5%) 1/30 (3%) |1/33 (3%) 0/39 (0%) 1/35 (3%) 3/34 (9%) | |FIRST INCIDENCE | 617 729 (T) 368 729 (T) |596 --- 665 610 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.597N P=0.718 P=0.466 P=0.755N |P=0.013 * P=0.110N P=0.628N P=0.171 | |POLY 3 | P=0.621N P=0.751 P=0.492 P=0.755N |P=0.012 * P=0.115N P=0.652N P=0.157 | |POLY 1.5 | P=0.626N P=0.760 P=0.502 P=0.754N |P=0.013 * P=0.115N P=0.655N P=0.161 | |POLY 6 | P=0.616N P=0.734 P=0.470 P=0.758N |P=0.012 * P=0.114N P=0.648N P=0.154 | |LOGISTIC REGRESSION| P=0.645 P=0.763N P=0.448 P=0.762N |P=0.016 * P=0.113N P=0.641N P=0.174 | |COCH-ARM / FISHERS | P=0.639N P=0.753N P=0.500 P=0.753N |P=0.015 * P=0.117N P=0.651N P=0.167 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Clitoral Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |1/49 (2%) 0/50 (0%) 4/49 (8%) 1/49 (2%) | |POLY-3 RATE (b) | |1/44.32 0/45.74 4/44.41 1/43.02 | |POLY-3 PERCENT (g) | |2.3% 0.0% 9.0% 2.3% | |TERMINAL (d) | |0/33 (0%) 0/39 (0%) 3/34 (9%) 1/33 (3%) | |FIRST INCIDENCE | |645 --- 702 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.547 P=0.495N P=0.196 P=0.758 | |POLY 3 | |P=0.548 P=0.494N P=0.179 P=0.754 | |POLY 1.5 | |P=0.557 P=0.495N P=0.178 P=0.757 | |POLY 6 | |P=0.534 P=0.492N P=0.181 P=0.751 | |LOGISTIC REGRESSION| |P=0.560 P=0.489N P=0.179 P=0.760N | |COCH-ARM / FISHERS | |P=0.570 P=0.495N P=0.181 P=0.753N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Clitoral Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |3/49 (6%) 2/50 (4%) 6/49 (12%) 3/49 (6%) | |POLY-3 RATE (b) | |3/44.01 2/45.74 6/44.30 3/43.17 | |POLY-3 PERCENT (g) | |6.8% 4.4% 13.5% 7.0% | |TERMINAL (d) | |3/33 (9%) 2/39 (5%) 6/34 (18%) 2/33 (6%) | |FIRST INCIDENCE | |730 (T) 730 (T) 730 (T) 690 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.505 P=0.424N P=0.254 P=0.660 | |POLY 3 | |P=0.522 P=0.482N P=0.244 P=0.654 | |POLY 1.5 | |P=0.531 P=0.487N P=0.241 P=0.656 | |POLY 6 | |P=0.511 P=0.475N P=0.250 P=0.651 | |LOGISTIC REGRESSION| |P=0.497 P=0.424N P=0.254 P=0.645 | |COCH-ARM / FISHERS | |P=0.544 P=0.490N P=0.243 P=0.661N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |5/49 (10%) 5/50 (10%) 6/49 (12%) 5/49 (10%) | |POLY-3 RATE (b) | |5/44.49 5/45.74 6/44.77 5/43.02 | |POLY-3 PERCENT (g) | |11.2% 10.9% 13.4% 11.6% | |TERMINAL (d) | |3/33 (9%) 5/39 (13%) 5/34 (15%) 5/33 (15%) | |FIRST INCIDENCE | |645 730 (T) 592 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.537 P=0.537N P=0.522 P=0.626 | |POLY 3 | |P=0.549 P=0.613N P=0.504 P=0.609 | |POLY 1.5 | |P=0.562 P=0.615N P=0.499 P=0.618 | |POLY 6 | |P=0.530 P=0.609N P=0.511 P=0.597 | |LOGISTIC REGRESSION| |P=0.547 P=0.601N P=0.500 P=0.611 | |COCH-ARM / FISHERS | |P=0.578N P=0.617N P=0.500 P=0.630N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Epididymis | | Atypia Cellular | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 29/50 (58%) 26/50 (52%) 25/50 (50%) 29/50 (58%) | | |POLY-3 RATE (b) | 29/44.66 26/42.58 25/43.18 29/46.03 | | |POLY-3 PERCENT (g) | 64.9% 61.1% 57.9% 63.0% | | |TERMINAL (d) | 19/30 (63%) 15/21 (71%) 12/21 (57%) 19/30 (63%) | | |FIRST INCIDENCE | 528 555 575 539 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.385N P=0.290 P=0.403 P=0.539N | | |POLY 3 | P=0.552N P=0.437N P=0.319N P=0.511N | | |POLY 1.5 | P=0.512 P=0.350N P=0.266N P=0.508N | | |POLY 6 | P=0.508N P=0.594N P=0.415N P=0.536N | | |LOGISTIC REGRESSION| P=0.532 P=0.367N P=0.280N P=0.507N | | |COCH-ARM / FISHERS | P=0.423 P=0.344N P=0.274N P=0.580N | | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Eye | | Cataract | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/3 (67%) 1/1 (100%) 1/1 (100%) 0/0 (0%) |4/5 (80%) 2/2 (100%) 3/4 (75%) 1/2 (50%) | |POLY-3 RATE (b) | 2/3.00 1/1.00 1/1.00 0/0.00 |4/4.54 2/2.00 3/4.00 1/1.58 | |POLY-3 PERCENT (g) | 66.7% 100.0% 100.0% 0.0% |88.0% 100.0% 75.0% 63.2% | |TERMINAL (d) | 1/2 (50%) 0/0 (0%) 1/1 (100%) 0/0 (0%) |3/3 (100%) 2/2 (100%) 2/3 (67%) 0/0 (0%) | |FIRST INCIDENCE | 679 631 729 (T) --- |646 730 (T) 725 603 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.373N P=0.700 P=0.736N P=0.507N |P=0.639 P=0.484N P=0.487N P=0.751 | |POLY 3 | (e) P=0.691 P=0.691 (e) |P=0.442N P=0.885 P=0.649N P=0.703N | |POLY 1.5 | (e) P=0.691 P=0.691 (e) |P=0.412N P=0.778 P=0.680N P=0.615N | |POLY 6 | (e) P=0.691 P=0.691 (e) |P=0.487N P=0.995 P=0.593N P=0.903N | |LOGISTIC REGRESSION| (e) (e) P=0.736N (e) |P=0.721N P=0.484N P=0.484N P=0.803 | |COCH-ARM / FISHERS | P=0.983 P=0.750 P=0.750 P=1.000 |P=0.365N P=0.714 P=0.722N P=0.524N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Eye | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/3 (0%) 0/1 (0%) 0/1 (0%) 0/0 (0%) |0/5 (0%) 0/2 (0%) 2/4 (50%) 0/2 (0%) | |POLY-3 RATE (b) | 0/2.81 0/0.65 0/1.00 0/0.00 |0/4.24 0/2.00 2/4.00 0/1.15 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 50.0% 0.0% | |TERMINAL (d) | 0/2 (0%) 0/0 (0%) 0/1 (0%) 0/0 (0%) |0/3 (0%) 0/2 (0%) 1/3 (33%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- --- 725 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.668 (e) P=0.249 (e) | |POLY 3 | (e) (e) (e) (e) |P=0.403 (e) P=0.176 (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.566 (e) P=0.158 (e) | |POLY 6 | (e) (e) (e) (e) |P=0.201 (e) P=0.207 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.534 (e) P=0.254 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.688 (e) P=0.167 (e) | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Eye: Retina | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/3 (67%) 1/1 (100%) 1/1 (100%) 0/0 (0%) |4/5 (80%) 2/2 (100%) 3/4 (75%) 1/2 (50%) | |POLY-3 RATE (b) | 2/3.00 1/1.00 1/1.00 0/0.00 |4/4.54 2/2.00 3/4.00 1/1.58 | |POLY-3 PERCENT (g) | 66.7% 100.0% 100.0% 0.0% |88.0% 100.0% 75.0% 63.2% | |TERMINAL (d) | 1/2 (50%) 0/0 (0%) 1/1 (100%) 0/0 (0%) |3/3 (100%) 2/2 (100%) 2/3 (67%) 0/0 (0%) | |FIRST INCIDENCE | 679 631 729 (T) --- |646 730 (T) 725 603 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.373N P=0.700 P=0.736N P=0.507N |P=0.639 P=0.484N P=0.487N P=0.751 | |POLY 3 | (e) P=0.691 P=0.691 (e) |P=0.442N P=0.885 P=0.649N P=0.703N | |POLY 1.5 | (e) P=0.691 P=0.691 (e) |P=0.412N P=0.778 P=0.680N P=0.615N | |POLY 6 | (e) P=0.691 P=0.691 (e) |P=0.487N P=0.995 P=0.593N P=0.903N | |LOGISTIC REGRESSION| (e) (e) P=0.736N (e) |P=0.721N P=0.484N P=0.484N P=0.803 | |COCH-ARM / FISHERS | P=0.983 P=0.750 P=0.750 P=1.000 |P=0.365N P=0.714 P=0.722N P=0.524N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 34/50 (68%) 31/50 (62%) 35/50 (70%) 36/50 (72%) |22/49 (45%) 16/50 (32%) 17/50 (34%) 16/50 (32%) | |POLY-3 RATE (b) | 34/44.50 31/45.10 35/44.96 36/46.91 |22/45.58 16/47.00 17/46.09 16/44.61 | |POLY-3 PERCENT (g) | 76.4% 68.7% 77.9% 76.7% |48.3% 34.0% 36.9% 35.9% | |TERMINAL (d) | 25/30 (83%) 14/21 (67%) 17/21 (81%) 24/30 (80%) |17/33 (52%) 13/39 (33%) 12/35 (34%) 14/34 (41%) | |FIRST INCIDENCE | 472 462 510 492 |610 572 665 603 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.463N P=0.242 P=0.073 P=0.459 |P=0.301N P=0.066N P=0.160N P=0.137N | |POLY 3 | P=0.386 P=0.273N P=0.537 P=0.586 |P=0.278N P=0.116N P=0.184N P=0.160N | |POLY 1.5 | P=0.339 P=0.255N P=0.564 P=0.551 |P=0.253N P=0.124N P=0.188N P=0.148N | |POLY 6 | P=0.444 P=0.322N P=0.489 P=0.602N |P=0.316N P=0.107N P=0.177N P=0.181N | |LOGISTIC REGRESSION| P=0.356 P=0.321N P=0.496 P=0.526 |P=0.258N P=0.124N P=0.169N P=0.148N | |COCH-ARM / FISHERS | P=0.258 P=0.338N P=0.500 P=0.414 |P=0.224N P=0.133N P=0.183N P=0.133N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Heart | | Thrombosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 4/50 (8%) 2/50 (4%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/40.89 2/39.74 4/40.31 2/42.47 |0/44.01 0/45.74 0/45.30 0/44.02 | |POLY-3 PERCENT (g) | 0.0% 5.0% 9.9% 4.7% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 1/21 (5%) 1/30 (3%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 679 603 720 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.436 P=0.195 P=0.047 * P=0.240 |(e) (e) (e) (e) | |POLY 3 | P=0.408 P=0.230 P=0.058 P=0.245 |(e) (e) (e) (e) | |POLY 1.5 | P=0.402 P=0.238 P=0.061 P=0.245 |(e) (e) (e) (e) | |POLY 6 | P=0.412 P=0.218 P=0.052 P=0.244 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.398 P=0.230 P=0.063 P=0.239 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.379 P=0.247 P=0.059 P=0.247 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Intestine Large, Cecum | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/49 (4%) 2/50 (4%) 3/50 (6%) 2/49 (4%) |0/49 (0%) 0/50 (0%) 1/49 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 2/40.03 2/40.01 3/39.80 2/41.62 |0/44.01 0/45.74 1/44.62 0/44.02 | |POLY-3 PERCENT (g) | 5.0% 5.0% 7.5% 4.8% |0.0% 0.0% 2.2% 0.0% | |TERMINAL (d) | 0/29 (0%) 0/21 (0%) 0/21 (0%) 0/29 (0%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 700 632 689 700 |--- --- 702 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.547N P=0.618 P=0.386 P=0.687N |P=0.800N (e) P=0.511 (e) | |POLY 3 | P=0.586N P=0.695 P=0.497 P=0.680N |P=0.787N (e) P=0.503 (e) | |POLY 1.5 | P=0.593N P=0.684N P=0.510 P=0.681N |P=0.785N (e) P=0.500 (e) | |POLY 6 | P=0.577N P=0.675 P=0.473 P=0.683N |P=0.789N (e) P=0.507 (e) | |LOGISTIC REGRESSION| P=0.587N P=0.691N P=0.477 P=0.684N |P=0.784N (e) P=0.500 (e) | |COCH-ARM / FISHERS | P=0.610N P=0.684N P=0.510 P=0.691N |P=0.783N (e) P=0.500 (e) | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Intestine Large, Cecum | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 2/49 (4%) |0/49 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/39.89 0/39.45 0/39.45 2/41.44 |0/44.01 0/45.74 0/44.51 0/44.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/29 (0%) 0/21 (0%) 0/21 (0%) 2/29 (7%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.060 (e) (e) P=0.238 |(e) (e) (e) (e) | |POLY 3 | P=0.043 * (e) (e) P=0.245 |(e) (e) (e) (e) | |POLY 1.5 | P=0.042 * (e) (e) P=0.245 |(e) (e) (e) (e) | |POLY 6 | P=0.044 * (e) (e) P=0.243 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.238 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.041 * (e) (e) P=0.247 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Intestine Large, Cecum: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/50 (0%) 2/49 (4%) |0/49 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/39.89 0/39.45 0/39.45 2/41.44 |0/44.01 0/45.74 0/44.51 0/44.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/29 (0%) 0/21 (0%) 0/21 (0%) 2/29 (7%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- 729 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.060 (e) (e) P=0.238 |(e) (e) (e) (e) | |POLY 3 | P=0.043 * (e) (e) P=0.245 |(e) (e) (e) (e) | |POLY 1.5 | P=0.042 * (e) (e) P=0.245 |(e) (e) (e) (e) | |POLY 6 | P=0.044 * (e) (e) P=0.243 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.238 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.041 * (e) (e) P=0.247 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Islets, Pancreatic | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 0/50 (0%) 1/49 (2%) 2/50 (4%) |0/49 (0%) 1/50 (2%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 5/42.19 0/39.45 1/38.88 2/42.44 |0/44.01 1/45.74 0/44.51 0/44.02 | |POLY-3 PERCENT (g) | 11.9% 0.0% 2.6% 4.7% |0.0% 2.2% 0.0% 0.0% | |TERMINAL (d) | 3/30 (10%) 0/21 (0%) 0/20 (0%) 2/30 (7%) |0/33 (0%) 1/39 (3%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 406 --- 602 729 (T) |--- 730 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.370N P=0.057N P=0.155N P=0.214N |P=0.595N P=0.533 (e) (e) | |POLY 3 | P=0.387N P=0.036N* P=0.120N P=0.213N |P=0.584N P=0.508 (e) (e) | |POLY 1.5 | P=0.404N P=0.032N* P=0.110N P=0.209N |P=0.584N P=0.506 (e) (e) | |POLY 6 | P=0.363N P=0.044N* P=0.138N P=0.220N |P=0.582N P=0.511 (e) (e) | |LOGISTIC REGRESSION| P=0.427N P=0.035N* P=0.112N P=0.220N |(e) P=0.533 (e) (e) | |COCH-ARM / FISHERS | P=0.418N P=0.028N* P=0.107N P=0.218N |P=0.585N P=0.505 (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Kidney | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 1/50 (2%) |0/49 (0%) 0/50 (0%) 1/49 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 0/40.89 1/39.45 2/39.46 1/42.44 |0/44.01 0/45.74 1/44.51 0/44.02 | |POLY-3 PERCENT (g) | 0.0% 2.5% 5.1% 2.4% |0.0% 0.0% 2.3% 0.0% | |TERMINAL (d) | 0/30 (0%) 1/21 (5%) 1/21 (5%) 1/30 (3%) |0/33 (0%) 0/39 (0%) 1/35 (3%) 0/34 (0%) | |FIRST INCIDENCE | --- 729 (T) 725 729 (T) |--- --- 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.545 P=0.429 P=0.167 P=0.500 |P=0.792N (e) P=0.512 (e) | |POLY 3 | P=0.524 P=0.493 P=0.229 P=0.507 |P=0.787N (e) P=0.502 (e) | |POLY 1.5 | P=0.519 P=0.500 P=0.236 P=0.507 |P=0.785N (e) P=0.500 (e) | |POLY 6 | P=0.526 P=0.480 P=0.215 P=0.506 |P=0.789N (e) P=0.506 (e) | |LOGISTIC REGRESSION| P=0.543 P=0.429 P=0.175 P=0.500 |(e) (e) P=0.512 (e) | |COCH-ARM / FISHERS | P=0.501 P=0.500 P=0.247 P=0.500 |P=0.783N (e) P=0.500 (e) | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Kidney | | Hydronephrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/49 (0%) 0/50 (0%) 1/49 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 0/40.89 0/39.45 0/39.45 2/42.83 |0/44.01 0/45.74 1/44.75 0/44.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 4.7% |0.0% 0.0% 2.2% 0.0% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 1/30 (3%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- 617 |--- --- 665 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.055 (e) (e) P=0.245 |P=0.792N (e) P=0.524 (e) | |POLY 3 | P=0.044 * (e) (e) P=0.247 |P=0.787N (e) P=0.503 (e) | |POLY 1.5 | P=0.043 * (e) (e) P=0.246 |P=0.785N (e) P=0.501 (e) | |POLY 6 | P=0.046 * (e) (e) P=0.247 |P=0.789N (e) P=0.508 (e) | |LOGISTIC REGRESSION| P=0.042 * (e) (e) P=0.238 |P=0.777N (e) P=0.511 (e) | |COCH-ARM / FISHERS | P=0.042 * (e) (e) P=0.247 |P=0.783N (e) P=0.500 (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 3/50 (6%) |0/49 (0%) 0/50 (0%) 2/49 (4%) 3/50 (6%) | |POLY-3 RATE (b) | 0/40.89 0/39.45 0/39.45 3/42.44 |0/44.01 0/45.74 2/45.47 3/44.70 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 7.1% |0.0% 0.0% 4.4% 6.7% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 3/30 (10%) |0/33 (0%) 0/39 (0%) 1/35 (3%) 1/34 (3%) | |FIRST INCIDENCE | --- --- --- 729 (T) |--- --- 232 592 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.017 * (e) (e) P=0.120 |P=0.036 * (e) P=0.246 P=0.126 | |POLY 3 | P=0.009 ** (e) (e) P=0.125 |P=0.037 * (e) P=0.244 P=0.121 | |POLY 1.5 | P=0.009 ** (e) (e) P=0.125 |P=0.037 * (e) P=0.241 P=0.122 | |POLY 6 | P=0.009 ** (e) (e) P=0.123 |P=0.036 * (e) P=0.249 P=0.121 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.120 |P=0.045 * (e) P=0.371 P=0.133 | |COCH-ARM / FISHERS | P=0.009 ** (e) (e) P=0.121 |P=0.039 * (e) P=0.247 P=0.125 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Kidney | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 13/50 (26%) 11/50 (22%) 13/50 (26%) 25/50 (50%) |0/49 (0%) 1/50 (2%) 1/49 (2%) 3/50 (6%) | |POLY-3 RATE (b) | 13/41.29 11/39.50 13/40.86 25/43.92 |0/44.01 1/45.74 1/44.58 3/44.02 | |POLY-3 PERCENT (g) | 31.5% 27.9% 31.8% 56.9% |0.0% 2.2% 2.2% 6.8% | |TERMINAL (d) | 12/30 (40%) 10/21 (48%) 9/21 (43%) 21/30 (70%) |0/33 (0%) 1/39 (3%) 0/35 (0%) 3/34 (9%) | |FIRST INCIDENCE | 617 716 575 602 |--- 730 (T) 711 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.004 ** P=0.391 P=0.248 P=0.008 ** |P=0.057 P=0.533 P=0.516 P=0.126 | |POLY 3 | P<0.001 ** P=0.454N P=0.582 P=0.012 * |P=0.062 P=0.508 P=0.503 P=0.118 | |POLY 1.5 | P<0.001 ** P=0.410N P=0.580N P=0.013 * |P=0.063 P=0.506 P=0.500 P=0.120 | |POLY 6 | P<0.001 ** P=0.539N P=0.533 P=0.012 * |P=0.060 P=0.511 P=0.506 P=0.117 | |LOGISTIC REGRESSION| P=0.002 ** P=0.532 P=0.481 P=0.011 * |P=0.054 P=0.533 P=0.502 P=0.126 | |COCH-ARM / FISHERS | P<0.001 ** P=0.408N P=0.590N P=0.011 * |P=0.066 P=0.505 P=0.500 P=0.125 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 48/50 (96%) 50/50 (100%) 50/50 (100%) 50/50 (100%)|46/49 (94%) 43/50 (86%) 45/49 (92%) 49/50 (98%) | |POLY-3 RATE (b) | 48/48.57 50/50.00 50/50.00 50/50.00 |46/48.69 43/49.04 45/47.82 49/49.53 | |POLY-3 PERCENT (g) | 98.8% 100.0% 100.0% 100.0% |94.5% 87.7% 94.1% 98.9% | |TERMINAL (d) | 30/30 (100%) 21/21 (100%) 21/21 (100%) 30/30 (100%)|31/33 (94%) 35/39 (90%) 33/35 (94%) 34/34 (100%) | |FIRST INCIDENCE | 216 462 368 266 |497 396 527 360 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.252N P=0.037 * P=0.040 * P=0.482 |P=0.115 P=0.065N P=0.325N P=0.413 | |POLY 3 | P=0.723 P=0.768 P=0.768 P=0.768 |P=0.061 P=0.195N P=0.644N P=0.235 | |POLY 1.5 | P=0.555 P=0.587 P=0.587 P=0.587 |P=0.068 P=0.180N P=0.622N P=0.261 | |POLY 6 | P=0.960 P=0.980 P=0.980 P=0.980 |P=0.058 P=0.224N P=0.649N P=0.209 | |LOGISTIC REGRESSION| P=0.375 P=0.498 P=0.439 P=0.424 |P=0.068 P=0.164N P=0.550N P=0.281 | |COCH-ARM / FISHERS | P=0.239 P=0.247 P=0.247 P=0.247 |P=0.084 P=0.167N P=0.500N P=0.301 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 45/50 (90%) 43/50 (86%) 43/50 (86%) |22/49 (45%) 49/50 (98%) 49/49 (100%) 50/50 (100%) | |POLY-3 RATE (b) | 3/40.97 45/48.49 43/47.80 43/48.49 |22/46.01 49/49.73 49/49.00 50/50.00 | |POLY-3 PERCENT (g) | 7.3% 92.8% 90.0% 88.7% |47.8% 98.5% 100.0% 100.0% | |TERMINAL (d) | 2/30 (7%) 19/21 (91%) 21/21 (100%) 26/30 (87%) |16/33 (49%) 39/39 (100%) 35/35 (100%) 34/34 (100%) | |FIRST INCIDENCE | 711 462 368 266 |497 396 232 360 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.002 ** 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 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Hyperplasia Oncocytic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/49 (0%) 0/50 (0%) 0/49 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/40.89 0/39.45 0/39.45 0/42.44 |0/44.01 0/45.74 0/44.51 2/44.43 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 4.5% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 0/30 (0%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 1/34 (3%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 610 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.038 * (e) (e) P=0.238 | |POLY 3 | (e) (e) (e) (e) |P=0.041 * (e) (e) P=0.239 | |POLY 1.5 | (e) (e) (e) (e) |P=0.041 * (e) (e) P=0.240 | |POLY 6 | (e) (e) (e) (e) |P=0.040 * (e) (e) P=0.239 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.045 * (e) (e) P=0.252 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.043 * (e) (e) P=0.253 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 35/50 (70%) 47/50 (94%) 49/50 (98%) 50/50 (100%)|45/49 (92%) 49/50 (98%) 49/49 (100%) 50/50 (100%) | |POLY-3 RATE (b) | 35/46.22 47/49.26 49/50.00 50/50.00 |45/48.36 49/49.73 49/49.00 50/50.00 | |POLY-3 PERCENT (g) | 75.7% 95.4% 98.0% 100.0% |93.1% 98.5% 100.0% 100.0% | |TERMINAL (d) | 21/30 (70%) 20/21 (95%) 20/21 (95%) 30/30 (100%)|31/33 (94%) 39/39 (100%) 35/35 (100%) 34/34 (100%) | |FIRST INCIDENCE | 216 462 368 266 |497 396 232 360 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.261 P=0.002 ** P<0.001 ** P=0.019 * |P=0.153 P=0.392N P=0.470 P=0.283 | |POLY 3 | P<0.001 ** P=0.004 ** P<0.001 ** P<0.001 ** |P=0.071 P=0.183 P=0.083 P=0.080 | |POLY 1.5 | P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** |P=0.061 P=0.180 P=0.071 P=0.068 | |POLY 6 | P<0.001 ** P=0.004 ** P<0.001 ** P<0.001 ** |P=0.089 P=0.178 P=0.102 P=0.099 | |LOGISTIC REGRESSION| P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** |P=0.052 P=0.174 P=0.059 P=0.055 | |COCH-ARM / FISHERS | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** |P=0.055 P=0.175 P=0.059 P=0.056 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Kidney: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 4/50 (8%) 3/50 (6%) 2/50 (4%) |2/49 (4%) 0/50 (0%) 1/49 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 4/40.89 4/39.69 3/39.56 2/42.78 |2/44.37 0/45.74 1/44.51 1/44.02 | |POLY-3 PERCENT (g) | 9.8% 10.1% 7.6% 4.7% |4.5% 0.0% 2.3% 2.3% | |TERMINAL (d) | 4/30 (13%) 3/21 (14%) 2/21 (10%) 1/30 (3%) |1/33 (3%) 0/39 (0%) 1/35 (3%) 1/34 (3%) | |FIRST INCIDENCE | 729 (T) 665 700 634 |630 --- 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.199N P=0.456 P=0.630 P=0.333N |P=0.630N P=0.221N P=0.484N P=0.501N | |POLY 3 | P=0.222N P=0.628 P=0.518N P=0.316N |P=0.618N P=0.230N P=0.499N P=0.503N | |POLY 1.5 | P=0.232N P=0.642N P=0.501N P=0.319N |P=0.614N P=0.232N P=0.501N P=0.499N | |POLY 6 | P=0.210N P=0.595 P=0.550N P=0.316N |P=0.624N P=0.228N P=0.495N P=0.508N | |LOGISTIC REGRESSION| P=0.213N P=0.533 P=0.634N P=0.322N |P=0.613N P=0.234N P=0.500N P=0.493N | |COCH-ARM / FISHERS | P=0.249N P=0.643N P=0.500N P=0.339N |P=0.610N P=0.242N P=0.500N P=0.492N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 5/50 (10%) 0/50 (0%) 11/50 (22%) |0/49 (0%) 0/50 (0%) 2/50 (4%) 4/50 (8%) | |POLY-3 RATE (b) | 5/41.29 5/39.64 0/39.45 11/42.78 |0/44.01 0/45.74 2/45.30 4/44.43 | |POLY-3 PERCENT (g) | 12.1% 12.6% 0.0% 25.7% |0.0% 0.0% 4.4% 9.0% | |TERMINAL (d) | 4/30 (13%) 4/21 (19%) 0/21 (0%) 10/30 (33%) |0/33 (0%) 0/39 (0%) 2/35 (6%) 3/34 (9%) | |FIRST INCIDENCE | 617 679 --- 634 |--- --- 730 (T) 610 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.034 * P=0.430 P=0.063N P=0.084 |P=0.009 ** (e) P=0.251 P=0.066 | |POLY 3 | P=0.015 * P=0.606 P=0.034N* P=0.092 |P=0.009 ** (e) P=0.244 P=0.061 | |POLY 1.5 | P=0.014 * P=0.629 P=0.031N* P=0.094 |P=0.010 * (e) P=0.242 P=0.062 | |POLY 6 | P=0.016 * P=0.562 P=0.040N* P=0.087 |P=0.009 ** (e) P=0.247 P=0.061 | |LOGISTIC REGRESSION| P=0.025 * P=0.550 P=0.039N* P=0.091 |P=0.010 * (e) P=0.251 P=0.065 | |COCH-ARM / FISHERS | P=0.015 * P=0.630N P=0.028N* P=0.086 |P=0.011 * (e) P=0.253 P=0.061 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 20/50 (40%) 18/50 (36%) 18/50 (36%) 23/50 (46%) |39/49 (80%) 44/50 (88%) 41/50 (82%) 45/50 (90%) | |POLY-3 RATE (b) | 20/41.39 18/40.07 18/39.60 23/42.95 |39/46.33 44/47.60 41/47.15 45/47.78 | |POLY-3 PERCENT (g) | 48.3% 44.9% 45.5% 53.6% |84.2% 92.4% 87.0% 94.2% | |TERMINAL (d) | 18/30 (60%) 15/21 (71%) 16/21 (76%) 21/30 (70%) |30/33 (91%) 38/39 (97%) 32/35 (91%) 34/34 (100%) | |FIRST INCIDENCE | 617 610 700 617 |527 572 592 529 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.453 P=0.215 P=0.191 P=0.323 |P=0.093 P=0.488N P=0.554N P=0.192 | |POLY 3 | P=0.268 P=0.465N P=0.485N P=0.393 |P=0.126 P=0.150 P=0.462 P=0.081 | |POLY 1.5 | P=0.249 P=0.411N P=0.425N P=0.395 |P=0.137 P=0.163 P=0.447 P=0.092 | |POLY 6 | P=0.293 P=0.575N P=0.587 P=0.374 |P=0.118 P=0.144 P=0.505 P=0.072 | |LOGISTIC REGRESSION| P=0.357 P=0.451 P=0.372 P=0.353 |P=0.072 P=0.216 P=0.538 P=0.064 | |COCH-ARM / FISHERS | P=0.212 P=0.418N P=0.418N P=0.343 |P=0.167 P=0.194 P=0.480 P=0.122 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 7/50 (14%) 9/50 (18%) 13/50 (26%) |2/49 (4%) 10/50 (20%) 4/50 (8%) 11/50 (22%) | |POLY-3 RATE (b) | 7/40.89 7/39.45 9/39.45 13/42.98 |2/44.01 10/45.74 4/45.30 11/44.63 | |POLY-3 PERCENT (g) | 17.1% 17.7% 22.8% 30.3% |4.5% 21.9% 8.8% 24.7% | |TERMINAL (d) | 7/30 (23%) 7/21 (33%) 9/21 (43%) 11/30 (37%) |2/33 (6%) 10/39 (26%) 4/35 (11%) 8/34 (24%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 590 |730 (T) 730 (T) 730 (T) 618 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.106 P=0.321 P=0.123 P=0.099 |P=0.027 * P=0.029 * P=0.363 P=0.010 * | |POLY 3 | P=0.067 P=0.587 P=0.359 P=0.121 |P=0.033 * P=0.016 * P=0.350 P=0.007 ** | |POLY 1.5 | P=0.061 P=0.614 P=0.389 P=0.121 |P=0.034 * P=0.015 * P=0.347 P=0.007 ** | |POLY 6 | P=0.075 P=0.534 P=0.305 P=0.119 |P=0.032 * P=0.017 * P=0.357 P=0.007 ** | |LOGISTIC REGRESSION| P=0.088 P=0.321 P=0.123 P=0.106 |P=0.025 * P=0.029 * P=0.363 P=0.008 ** | |COCH-ARM / FISHERS | P=0.051 P=0.613N P=0.393 P=0.105 |P=0.038 * P=0.015 * P=0.349 P=0.008 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 10/50 (20%) 11/50 (22%) 10/50 (20%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 7/41.06 10/40.30 11/40.92 10/42.69 |0/44.01 0/45.74 0/45.30 0/44.02 | |POLY-3 PERCENT (g) | 17.1% 24.8% 26.9% 23.4% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 6/30 (20%) 5/21 (24%) 6/21 (29%) 7/30 (23%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 686 631 575 702 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.519 P=0.116 P=0.080 P=0.303 |(e) (e) (e) (e) | |POLY 3 | P=0.420 P=0.277 P=0.207 P=0.325 |(e) (e) (e) (e) | |POLY 1.5 | P=0.406 P=0.301 P=0.223 P=0.324 |(e) (e) (e) (e) | |POLY 6 | P=0.433 P=0.237 P=0.179 P=0.319 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.450 P=0.196 P=0.170 P=0.304 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.369 P=0.298 P=0.218 P=0.298 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 8/50 (16%) 6/50 (12%) 10/50 (20%) |18/49 (37%) 10/50 (20%) 18/50 (36%) 27/50 (54%) | |POLY-3 RATE (b) | 6/40.89 8/39.70 6/39.45 10/42.83 |18/46.11 10/46.17 18/45.66 27/45.13 | |POLY-3 PERCENT (g) | 14.7% 20.2% 15.2% 23.4% |39.0% 21.7% 39.4% 59.8% | |TERMINAL (d) | 6/30 (20%) 6/21 (29%) 6/21 (29%) 9/30 (30%) |12/33 (36%) 8/39 (21%) 16/35 (46%) 22/34 (65%) | |FIRST INCIDENCE | 729 (T) 679 729 (T) 617 |497 656 665 610 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.302 P=0.158 P=0.355 P=0.199 |P=0.002 ** P=0.031N* P=0.498N P=0.076 | |POLY 3 | P=0.225 P=0.361 P=0.597 P=0.231 |P<0.001 ** P=0.053N P=0.570 P=0.033 * | |POLY 1.5 | P=0.213 P=0.388 P=0.620 P=0.230 |P<0.001 ** P=0.053N P=0.580 P=0.043 * | |POLY 6 | P=0.238 P=0.314 P=0.552 P=0.228 |P<0.001 ** P=0.052N P=0.563 P=0.025 * | |LOGISTIC REGRESSION| P=0.267 P=0.209 P=0.355 P=0.210 |P=0.002 ** P=0.052N P=0.549N P=0.052 | |COCH-ARM / FISHERS | P=0.189 P=0.387 P=0.620N P=0.207 |P=0.003 ** P=0.052N P=0.553N P=0.064 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/49 (4%) 0/50 (0%) 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 2/42.72 0/39.45 0/39.45 0/42.44 |2/44.11 0/45.74 2/46.27 2/44.76 | |POLY-3 PERCENT (g) | 4.7% 0.0% 0.0% 0.0% |4.5% 0.0% 4.3% 4.5% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 0/30 (0%) |1/33 (3%) 0/39 (0%) 1/35 (3%) 0/34 (0%) | |FIRST INCIDENCE | 122 --- --- --- |704 --- 232 592 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.238N P=0.233N P=0.237N P=0.235N |P=0.420 P=0.213N P=0.679N P=0.690N | |POLY 3 | P=0.222N P=0.255N P=0.255N P=0.238N |P=0.427 P=0.229N P=0.677N P=0.689N | |POLY 1.5 | P=0.231N P=0.245N P=0.245N P=0.237N |P=0.430 P=0.231N P=0.681N P=0.688N | |POLY 6 | P=0.210N P=0.272N P=0.271N P=0.241N |P=0.423 P=0.226N P=0.672N P=0.689N | |LOGISTIC REGRESSION| P=0.450N P=0.762N P=0.635N P=0.540N |P=0.485 P=0.227N P=0.618N P=0.671N | |COCH-ARM / FISHERS | P=0.239N P=0.247N P=0.247N P=0.247N |P=0.435 P=0.242N P=0.684N P=0.684N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Hepatodiaphragmatic Nodule | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 5/50 (10%) 2/50 (4%) 4/50 (8%) |3/49 (6%) 9/50 (18%) 7/50 (14%) 7/50 (14%) | |POLY-3 RATE (b) | 3/41.84 5/40.43 2/39.56 4/43.12 |3/44.62 9/46.23 7/45.75 7/44.56 | |POLY-3 PERCENT (g) | 7.2% 12.4% 5.1% 9.3% |6.7% 19.5% 15.3% 15.7% | |TERMINAL (d) | 2/30 (7%) 2/21 (10%) 1/21 (5%) 2/30 (7%) |1/33 (3%) 7/39 (18%) 4/35 (11%) 4/34 (12%) | |FIRST INCIDENCE | 284 610 700 597 |544 605 674 657 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.568N P=0.259 P=0.612N P=0.507 |P=0.338 P=0.105 P=0.190 P=0.173 | |POLY 3 | P=0.573 P=0.336 P=0.526N P=0.517 |P=0.355 P=0.067 P=0.167 P=0.156 | |POLY 1.5 | P=0.565 P=0.353 P=0.508N P=0.515 |P=0.364 P=0.066 P=0.165 P=0.160 | |POLY 6 | P=0.584 P=0.310 P=0.554N P=0.517 |P=0.346 P=0.070 P=0.173 P=0.153 | |LOGISTIC REGRESSION| P=0.541 P=0.343 P=0.510N P=0.469 |P=0.366 P=0.067 P=0.167 P=0.166 | |COCH-ARM / FISHERS | P=0.547 P=0.357 P=0.500N P=0.500 |P=0.380 P=0.065 P=0.167 P=0.167 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Mixed Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 2/50 (4%) 2/50 (4%) |15/49 (31%) 12/50 (24%) 9/50 (18%) 11/50 (22%) | |POLY-3 RATE (b) | 0/40.89 2/39.45 2/40.63 2/42.74 |15/45.32 12/46.02 9/45.30 11/45.12 | |POLY-3 PERCENT (g) | 0.0% 5.1% 4.9% 4.7% |33.1% 26.1% 19.9% 24.4% | |TERMINAL (d) | 0/30 (0%) 2/21 (10%) 0/21 (0%) 1/30 (3%) |11/33 (33%) 11/39 (28%) 9/35 (26%) 7/34 (21%) | |FIRST INCIDENCE | --- 729 (T) 368 645 |497 656 730 (T) 590 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.387 P=0.163 P=0.237 P=0.243 |P=0.331N P=0.189N P=0.091N P=0.241N | |POLY 3 | P=0.364 P=0.229 P=0.235 P=0.247 |P=0.293N P=0.306N P=0.115N P=0.246N | |POLY 1.5 | P=0.358 P=0.237 P=0.240 P=0.246 |P=0.286N P=0.308N P=0.115N P=0.241N | |POLY 6 | P=0.367 P=0.214 P=0.224 P=0.246 |P=0.301N P=0.300N P=0.114N P=0.251N | |LOGISTIC REGRESSION| P=0.319 P=0.163 P=0.150 P=0.242 |P=0.304N P=0.286N P=0.103N P=0.236N | |COCH-ARM / FISHERS | P=0.339 P=0.247 P=0.247 P=0.247 |P=0.275N P=0.304N P=0.109N P=0.228N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 4/50 (8%) 3/50 (6%) 9/50 (18%) |4/49 (8%) 5/50 (10%) 6/50 (12%) 1/50 (2%) | |POLY-3 RATE (b) | 6/41.29 4/39.45 3/39.45 9/42.86 |4/44.62 5/45.74 6/45.85 1/44.17 | |POLY-3 PERCENT (g) | 14.5% 10.1% 7.6% 21.0% |9.0% 10.9% 13.1% 2.3% | |TERMINAL (d) | 5/30 (17%) 4/21 (19%) 3/21 (14%) 8/30 (27%) |2/33 (6%) 5/39 (13%) 4/35 (11%) 0/34 (0%) | |FIRST INCIDENCE | 617 729 (T) 729 (T) 607 |646 730 (T) 648 690 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.172 P=0.583N P=0.416N P=0.291 |P=0.114N P=0.586 P=0.423 P=0.183N | |POLY 3 | P=0.121 P=0.397N P=0.263N P=0.312 |P=0.108N P=0.516 P=0.387 P=0.181N | |POLY 1.5 | P=0.113 P=0.372N P=0.245N P=0.312 |P=0.104N P=0.514 P=0.382 P=0.178N | |POLY 6 | P=0.131 P=0.445N P=0.298N P=0.305 |P=0.114N P=0.519 P=0.394 P=0.186N | |LOGISTIC REGRESSION| P=0.145 P=0.476N P=0.317N P=0.306 |P=0.103N P=0.522 P=0.382 P=0.169N | |COCH-ARM / FISHERS | P=0.103 P=0.370N P=0.243N P=0.288 |P=0.099N P=0.513 P=0.383 P=0.175N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 2/50 (4%) 0/50 (0%) |4/49 (8%) 4/50 (8%) 3/50 (6%) 0/50 (0%) | |POLY-3 RATE (b) | 2/41.87 2/39.79 2/40.57 0/42.44 |4/44.01 4/46.19 3/45.30 0/44.02 | |POLY-3 PERCENT (g) | 4.8% 5.0% 4.9% 0.0% |9.1% 8.7% 6.6% 0.0% | |TERMINAL (d) | 1/30 (3%) 0/21 (0%) 0/21 (0%) 0/30 (0%) |4/33 (12%) 3/39 (8%) 3/35 (9%) 0/34 (0%) | |FIRST INCIDENCE | 216 638 483 --- |730 (T) 600 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.149N P=0.620 P=0.670 P=0.238N |P=0.042N* P=0.558N P=0.467N P=0.059N | |POLY 3 | P=0.148N P=0.676 P=0.683 P=0.234N |P=0.041N* P=0.617N P=0.484N P=0.060N | |POLY 1.5 | P=0.151N P=0.689 P=0.692 P=0.233N |P=0.040N* P=0.624N P=0.489N P=0.059N | |POLY 6 | P=0.145N P=0.654 P=0.666 P=0.236N |P=0.043N* P=0.604N P=0.477N P=0.061N | |LOGISTIC REGRESSION| P=0.200N P=0.640 P=0.588 P=0.336N |P=0.041N* P=0.622N P=0.467N (e) | |COCH-ARM / FISHERS | P=0.156N P=0.691N P=0.691N P=0.247N |P=0.038N* P=0.631N P=0.489N P=0.056N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 24 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 33/50 (66%) 24/50 (48%) 20/50 (40%) 14/50 (28%) |1/49 (2%) 0/50 (0%) 4/50 (8%) 1/50 (2%) | |POLY-3 RATE (b) | 33/44.89 24/42.29 20/41.95 14/44.20 |1/44.11 0/45.74 4/46.60 1/44.26 | |POLY-3 PERCENT (g) | 73.5% 56.8% 47.7% 31.7% |2.3% 0.0% 8.6% 2.3% | |TERMINAL (d) | 24/30 (80%) 12/21 (57%) 10/21 (48%) 7/30 (23%) |0/33 (0%) 0/39 (0%) 1/35 (3%) 0/34 (0%) | |FIRST INCIDENCE | 216 506 533 607 |704 --- 232 665 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001N** P=0.487N P=0.186N P<0.001N** |P=0.554 P=0.484N P=0.198 P=0.754 | |POLY 3 | P<0.001N** P=0.064N P=0.008N** P<0.001N** |P=0.563 P=0.493N P=0.196 P=0.760N | |POLY 1.5 | P<0.001N** P=0.049N* P=0.006N** P<0.001N** |P=0.569 P=0.494N P=0.191 P=0.759N | |POLY 6 | P<0.001N** P=0.102N P=0.013N* P<0.001N** |P=0.554 P=0.490N P=0.202 P=0.760 | |LOGISTIC REGRESSION| P<0.001N** P=0.048N* P=0.007N** P<0.001N** |P=0.624 P=0.495N P=0.227 P=0.754N | |COCH-ARM / FISHERS | P<0.001N** P=0.053N P=0.008N** P<0.001N** |P=0.577 P=0.495N P=0.187 P=0.747N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver: Hepatocyte | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 3/50 (6%) 4/50 (8%) 2/50 (4%) |3/49 (6%) 2/50 (4%) 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 3/41.22 3/39.83 4/40.42 2/42.59 |3/44.64 2/46.39 2/45.63 2/44.70 | |POLY-3 PERCENT (g) | 7.3% 7.5% 9.9% 4.7% |6.7% 4.3% 4.4% 4.5% | |TERMINAL (d) | 0/30 (0%) 1/21 (5%) 1/21 (5%) 0/30 (0%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 679 679 602 700 |630 634 674 603 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.350N P=0.541 P=0.403 P=0.500N |P=0.517N P=0.478N P=0.482N P=0.516N | |POLY 3 | P=0.371N P=0.647 P=0.489 P=0.485N |P=0.497N P=0.482N P=0.490N P=0.499N | |POLY 1.5 | P=0.379N P=0.662N P=0.503 P=0.485N |P=0.492N P=0.487N P=0.492N P=0.496N | |POLY 6 | P=0.362N P=0.618 P=0.462 P=0.490N |P=0.505N P=0.476N P=0.486N P=0.504N | |LOGISTIC REGRESSION| P=0.379N P=0.641 P=0.498 P=0.485N |P=0.456N P=0.491N P=0.481N P=0.453N | |COCH-ARM / FISHERS | P=0.399N P=0.661N P=0.500 P=0.500N |P=0.485N P=0.490N P=0.490N P=0.490N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 25 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Liver: Kupffer Cell | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 4/50 (8%) |2/49 (4%) 2/50 (4%) 3/50 (6%) 1/50 (2%) | |POLY-3 RATE (b) | 1/40.89 1/39.86 2/39.94 4/43.24 |2/44.54 2/46.05 3/45.55 1/44.26 | |POLY-3 PERCENT (g) | 2.5% 2.5% 5.0% 9.3% |4.5% 4.3% 6.6% 2.3% | |TERMINAL (d) | 1/30 (3%) 0/21 (0%) 0/21 (0%) 1/30 (3%) |0/33 (0%) 1/39 (3%) 2/35 (6%) 0/34 (0%) | |FIRST INCIDENCE | 729 (T) 610 617 607 |630 646 665 665 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.105 P=0.724 P=0.427 P=0.192 |P=0.396N P=0.666N P=0.526 P=0.511N | |POLY 3 | P=0.086 P=0.755 P=0.492 P=0.195 |P=0.389N P=0.682N P=0.510 P=0.502N | |POLY 1.5 | P=0.082 P=0.760N P=0.501 P=0.193 |P=0.382N P=0.684N P=0.508 P=0.499N | |POLY 6 | P=0.093 P=0.743 P=0.474 P=0.197 |P=0.397N P=0.678N P=0.514 P=0.507N | |LOGISTIC REGRESSION| P=0.074 P=0.762N P=0.496 P=0.185 |P=0.363N P=0.691N P=0.513 P=0.466N | |COCH-ARM / FISHERS | P=0.074 P=0.753N P=0.500 P=0.181 |P=0.373N P=0.684N P=0.510 P=0.492N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lung | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 1/50 (2%) |3/49 (6%) 1/50 (2%) 2/50 (4%) 5/50 (10%) | |POLY-3 RATE (b) | 0/40.89 1/40.19 2/40.27 1/42.51 |3/44.47 1/46.58 2/46.27 5/44.02 | |POLY-3 PERCENT (g) | 0.0% 2.5% 5.0% 2.4% |6.8% 2.2% 4.3% 11.4% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 0/30 (0%) |2/33 (6%) 0/39 (0%) 1/35 (3%) 5/34 (15%) | |FIRST INCIDENCE | --- 464 533 711 |596 396 232 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.523 P=0.513 P=0.224 P=0.506 |P=0.111 P=0.275N P=0.484N P=0.371 | |POLY 3 | P=0.522 P=0.497 P=0.233 P=0.508 |P=0.110 P=0.289N P=0.482N P=0.350 | |POLY 1.5 | P=0.518 P=0.502 P=0.239 P=0.507 |P=0.115 P=0.293N P=0.486N P=0.357 | |POLY 6 | P=0.526 P=0.485 P=0.223 P=0.507 |P=0.104 P=0.284N P=0.478N P=0.342 | |LOGISTIC REGRESSION| P=0.452 P=0.365 P=0.217 P=0.506 |P=0.145 P=0.271N P=0.406N P=0.354 | |COCH-ARM / FISHERS | P=0.501 P=0.500 P=0.247 P=0.500 |P=0.123 P=0.301N P=0.490N P=0.369 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 26 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 26/50 (52%) 28/50 (56%) 27/50 (54%) 35/50 (70%) |38/49 (78%) 37/50 (74%) 34/50 (68%) 32/50 (64%) | |POLY-3 RATE (b) | 26/41.59 28/43.53 27/44.61 35/45.67 |38/47.29 37/48.27 34/47.56 32/47.03 | |POLY-3 PERCENT (g) | 62.5% 64.3% 60.5% 76.6% |80.4% 76.7% 71.5% 68.1% | |TERMINAL (d) | 21/30 (70%) 14/21 (67%) 12/21 (57%) 24/30 (80%) |26/33 (79%) 32/39 (82%) 27/35 (77%) 24/34 (71%) | |FIRST INCIDENCE | 617 584 373 449 |497 396 539 529 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.221 P=0.059 P=0.106 P=0.069 |P=0.217N P=0.162N P=0.184N P=0.164N | |POLY 3 | P=0.060 P=0.521 P=0.513N P=0.101 |P=0.106N P=0.422N P=0.215N P=0.120N | |POLY 1.5 | P=0.050 P=0.511 P=0.544N P=0.083 |P=0.099N P=0.423N P=0.219N P=0.114N | |POLY 6 | P=0.078 P=0.524 P=0.494N P=0.126 |P=0.116N P=0.430N P=0.206N P=0.131N | |LOGISTIC REGRESSION| P=0.058 P=0.273 P=0.449 P=0.055 |P=0.103N P=0.416N P=0.200N P=0.116N | |COCH-ARM / FISHERS | P=0.035 * P=0.421 P=0.500 P=0.050 |P=0.086N P=0.430N P=0.200N P=0.104N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lung | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |1/49 (2%) 1/50 (2%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 1/41.89 0/39.45 0/39.45 2/42.44 |1/44.01 1/45.90 1/45.30 0/44.02 | |POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 4.7% |2.3% 2.2% 2.2% 0.0% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 2/30 (7%) |1/33 (3%) 0/39 (0%) 1/35 (3%) 0/34 (0%) | |FIRST INCIDENCE | 122 --- --- 729 (T) |730 (T) 690 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.222 P=0.500N P=0.500N P=0.500 |P=0.335N P=0.730N P=0.749N P=0.494N | |POLY 3 | P=0.201 P=0.512N P=0.512N P=0.505 |P=0.328N P=0.751N P=0.754N P=0.500N | |POLY 1.5 | P=0.196 P=0.504N P=0.505N P=0.505 |P=0.326N P=0.754N P=0.756N P=0.499N | |POLY 6 | P=0.209 P=0.526N P=0.525N P=0.501 |P=0.332N P=0.747N P=0.751N P=0.502N | |LOGISTIC REGRESSION| P=0.123 (e) (e) P=0.382 |P=0.328N P=0.756N P=0.749N (e) | |COCH-ARM / FISHERS | P=0.191 P=0.500N P=0.500N P=0.500 |P=0.321N P=0.747N P=0.747N P=0.495N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 27 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 1/50 (2%) 2/50 (4%) 5/50 (10%) |3/49 (6%) 4/50 (8%) 0/50 (0%) 4/50 (8%) | |POLY-3 RATE (b) | 5/41.61 1/39.45 2/39.76 5/42.55 |3/44.18 4/46.05 0/45.30 4/44.02 | |POLY-3 PERCENT (g) | 12.0% 2.5% 5.0% 11.8% |6.8% 8.7% 0.0% 9.1% | |TERMINAL (d) | 3/30 (10%) 1/21 (5%) 0/21 (0%) 4/30 (13%) |2/33 (6%) 3/39 (8%) 0/35 (0%) 4/34 (12%) | |FIRST INCIDENCE | 528 729 (T) 673 700 |685 646 --- 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.369 P=0.180N P=0.333N P=0.624N |P=0.431 P=0.571 P=0.116N P=0.510 | |POLY 3 | P=0.318 P=0.112N P=0.233N P=0.617N |P=0.448 P=0.523 P=0.114N P=0.498 | |POLY 1.5 | P=0.305 P=0.103N P=0.219N P=0.614N |P=0.453 P=0.517 P=0.115N P=0.503 | |POLY 6 | P=0.337 P=0.132N P=0.260N P=0.627N |P=0.440 P=0.532 P=0.112N P=0.491 | |LOGISTIC REGRESSION| P=0.326 P=0.108N P=0.221N P=0.610N |P=0.437 P=0.519 P=0.114N P=0.491 | |COCH-ARM / FISHERS | P=0.290 P=0.102N P=0.218N P=0.630N |P=0.461 P=0.511 P=0.117N P=0.511 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 3/50 (6%) 2/48 (4%) 1/50 (2%) |1/49 (2%) 2/50 (4%) 6/50 (12%) 6/50 (12%) | |POLY-3 RATE (b) | 0/39.89 3/39.64 2/38.55 1/42.44 |1/44.01 2/46.05 6/45.41 6/44.64 | |POLY-3 PERCENT (g) | 0.0% 7.6% 5.2% 2.4% |2.3% 4.3% 13.2% 13.4% | |TERMINAL (d) | 0/29 (0%) 2/21 (10%) 0/20 (0%) 1/30 (3%) |1/33 (3%) 1/39 (3%) 5/35 (14%) 3/34 (9%) | |FIRST INCIDENCE | --- 679 624 729 (T) |730 (T) 646 702 646 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.520N P=0.078 P=0.230 P=0.507 |P=0.038 * P=0.544 P=0.069 P=0.065 | |POLY 3 | P=0.546N P=0.117 P=0.229 P=0.512 |P=0.041 * P=0.516 P=0.061 P=0.058 | |POLY 1.5 | P=0.548N P=0.123 P=0.234 P=0.512 |P=0.042 * P=0.511 P=0.059 P=0.058 | |POLY 6 | P=0.549N P=0.106 P=0.219 P=0.511 |P=0.039 * P=0.523 P=0.063 P=0.058 | |LOGISTIC REGRESSION| P=0.548N P=0.100 P=0.227 P=0.507 |P=0.041 * P=0.507 P=0.066 P=0.059 | |COCH-ARM / FISHERS | P=0.566N P=0.125 P=0.242 P=0.505 |P=0.046 * P=0.508 P=0.059 P=0.059 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 28 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 1/48 (2%) 2/50 (4%) |2/49 (4%) 4/50 (8%) 4/50 (8%) 4/50 (8%) | |POLY-3 RATE (b) | 0/39.89 0/39.45 1/38.57 2/42.44 |2/45.15 4/45.74 4/46.52 4/44.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.6% 4.7% |4.4% 8.8% 8.6% 9.1% | |TERMINAL (d) | 0/29 (0%) 0/21 (0%) 0/20 (0%) 2/30 (7%) |0/33 (0%) 4/39 (10%) 2/35 (6%) 4/34 (12%) | |FIRST INCIDENCE | --- --- 483 729 (T) |497 730 (T) 232 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.113 (e) P=0.513 P=0.245 |P=0.372 P=0.393 P=0.359 P=0.348 | |POLY 3 | P=0.096 (e) P=0.493 P=0.251 |P=0.369 P=0.343 P=0.351 P=0.325 | |POLY 1.5 | P=0.093 (e) P=0.498 P=0.250 |P=0.380 P=0.344 P=0.349 P=0.334 | |POLY 6 | P=0.099 (e) P=0.483 P=0.249 |P=0.354 P=0.345 P=0.354 P=0.315 | |LOGISTIC REGRESSION| P=0.081 (e) P=0.406 P=0.245 |P=0.430 P=0.342 P=0.400 P=0.370 | |COCH-ARM / FISHERS | P=0.088 (e) P=0.495 P=0.253 |P=0.398 P=0.349 P=0.349 P=0.349 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 0/50 (0%) 1/48 (2%) 0/50 (0%) |1/49 (2%) 0/50 (0%) 2/50 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 1/39.89 0/39.45 1/37.86 0/42.44 |1/44.01 0/45.74 2/46.27 1/44.90 | |POLY-3 PERCENT (g) | 2.5% 0.0% 2.6% 0.0% |2.3% 0.0% 4.3% 2.2% | |TERMINAL (d) | 1/29 (3%) 0/21 (0%) 1/20 (5%) 0/30 (0%) |1/33 (3%) 0/39 (0%) 1/35 (3%) 0/34 (0%) | |FIRST INCIDENCE | 729 (T) --- 729 (T) --- |730 (T) --- 232 360 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.423N P=0.564N P=0.677 P=0.493N |P=0.552 P=0.467N P=0.514 P=0.757N | |POLY 3 | P=0.441N P=0.502N P=0.749 P=0.488N |P=0.558 P=0.492N P=0.517 P=0.756N | |POLY 1.5 | P=0.449N P=0.495N P=0.756 P=0.488N |P=0.561 P=0.494N P=0.513 P=0.756N | |POLY 6 | P=0.430N P=0.515N P=0.736 P=0.489N |P=0.551 P=0.489N P=0.523 P=0.757N | |LOGISTIC REGRESSION| P=0.423N (e) P=0.677 (e) |P=0.662 (e) P=0.630 P=0.667N | |COCH-ARM / FISHERS | P=0.456N P=0.495N P=0.747 P=0.495N |P=0.563 P=0.495N P=0.508 P=0.747N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 29 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 2/50 (4%) 0/48 (0%) 2/50 (4%) |18/49 (37%) 19/50 (38%) 21/50 (42%) 25/50 (50%) | |POLY-3 RATE (b) | 0/39.89 2/39.45 0/37.86 2/42.67 |18/45.06 19/45.74 21/46.01 25/44.54 | |POLY-3 PERCENT (g) | 0.0% 5.1% 0.0% 4.7% |40.0% 41.5% 45.6% 56.1% | |TERMINAL (d) | 0/29 (0%) 2/21 (10%) 0/20 (0%) 1/30 (3%) |12/33 (36%) 19/39 (49%) 16/35 (46%) 22/34 (65%) | |FIRST INCIDENCE | --- 729 (T) --- 668 |630 730 (T) 665 646 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.335 P=0.170 (e) P=0.243 |P=0.052 P=0.437N P=0.435 P=0.136 | |POLY 3 | P=0.299 P=0.234 (e) P=0.252 |P=0.057 P=0.524 P=0.367 P=0.087 | |POLY 1.5 | P=0.297 P=0.242 (e) P=0.251 |P=0.068 P=0.526 P=0.362 P=0.103 | |POLY 6 | P=0.298 P=0.220 (e) P=0.252 |P=0.044 * P=0.519 P=0.378 P=0.069 | |LOGISTIC REGRESSION| P=0.316 P=0.170 (e) P=0.250 |P=0.042 * P=0.575N P=0.398 P=0.088 | |COCH-ARM / FISHERS | P=0.285 P=0.253 (e) P=0.253 |P=0.088 P=0.531 P=0.371 P=0.129 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 4/50 (8%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 1/41.72 1/40.19 2/40.19 4/42.47 |0/44.24 0/45.74 2/46.27 1/44.48 | |POLY-3 PERCENT (g) | 2.4% 2.5% 5.0% 9.4% |0.0% 0.0% 4.3% 2.3% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 3/30 (10%) |0/33 (0%) 0/39 (0%) 1/35 (3%) 0/34 (0%) | |FIRST INCIDENCE | 406 464 603 720 |--- --- 232 592 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.104 P=0.746N P=0.498 P=0.186 |P=0.353 (e) P=0.246 P=0.504 | |POLY 3 | P=0.080 P=0.753 P=0.487 P=0.183 |P=0.352 (e) P=0.247 P=0.501 | |POLY 1.5 | P=0.078 P=0.760 P=0.498 P=0.185 |P=0.353 (e) P=0.243 P=0.501 | |POLY 6 | P=0.082 P=0.738 P=0.469 P=0.179 |P=0.349 (e) P=0.252 P=0.502 | |LOGISTIC REGRESSION| P=0.059 P=0.611 P=0.428 P=0.175 |P=0.384 (e) P=0.318 P=0.525 | |COCH-ARM / FISHERS | P=0.074 P=0.753N P=0.500 P=0.181 |P=0.355 (e) P=0.247 P=0.500 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 30 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mediastinal | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 4/50 (8%) 2/50 (4%) |1/50 (2%) 1/50 (2%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 0/40.89 2/40.14 4/40.60 2/42.44 |1/44.24 1/46.09 1/45.30 0/44.02 | |POLY-3 PERCENT (g) | 0.0% 5.0% 9.9% 4.7% |2.3% 2.2% 2.2% 0.0% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 2/30 (7%) |1/33 (3%) 0/39 (0%) 1/35 (3%) 0/34 (0%) | |FIRST INCIDENCE | --- 631 603 729 (T) |730 (T) 634 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.430 P=0.228 P=0.054 P=0.238 |P=0.333N P=0.737N P=0.749N P=0.494N | |POLY 3 | P=0.406 P=0.232 P=0.059 P=0.245 |P=0.330N P=0.752N P=0.755N P=0.501N | |POLY 1.5 | P=0.401 P=0.239 P=0.061 P=0.245 |P=0.328N P=0.756N P=0.758N P=0.501N | |POLY 6 | P=0.408 P=0.221 P=0.054 P=0.243 |P=0.333N P=0.746N P=0.752N P=0.502N | |LOGISTIC REGRESSION| P=0.378 P=0.228 P=0.062 P=0.238 |P=0.324N P=0.756 P=0.749N (e) | |COCH-ARM / FISHERS | P=0.379 P=0.247 P=0.059 P=0.247 |P=0.324N P=0.753N P=0.753N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 6/50 (12%) |0/49 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/40.89 0/39.45 0/39.45 6/43.89 |0/44.01 0/45.74 0/44.51 0/44.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 13.7% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 2/30 (7%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- 602 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) (e) P=0.023 * |(e) (e) (e) (e) | |POLY 3 | P<0.001 ** (e) (e) P=0.019 * |(e) (e) (e) (e) | |POLY 1.5 | P<0.001 ** (e) (e) P=0.018 * |(e) (e) (e) (e) | |POLY 6 | P<0.001 ** (e) (e) P=0.020 * |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.016 * |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.013 * |(e) (e) (e) (e) | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 31 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 2/50 (4%) 2/50 (4%) |2/49 (4%) 5/50 (10%) 2/49 (4%) 4/50 (8%) | |POLY-3 RATE (b) | 2/41.06 2/40.19 2/39.88 2/42.47 |2/44.37 5/46.19 2/45.49 4/44.73 | |POLY-3 PERCENT (g) | 4.9% 5.0% 5.0% 4.7% |4.5% 10.8% 4.4% 8.9% | |TERMINAL (d) | 1/30 (3%) 1/21 (5%) 1/21 (5%) 1/30 (3%) |1/33 (3%) 4/39 (10%) 0/35 (0%) 1/34 (3%) | |FIRST INCIDENCE | 686 464 603 720 |630 600 232 602 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.563N P=0.610 P=0.615 P=0.692 |P=0.419 P=0.273 P=0.679N P=0.338 | |POLY 3 | P=0.603N P=0.687 P=0.684 P=0.682N |P=0.439 P=0.233 P=0.685N P=0.341 | |POLY 1.5 | P=0.608N P=0.691N P=0.694N P=0.682N |P=0.443 P=0.229 P=0.688N P=0.343 | |POLY 6 | P=0.596N P=0.665 P=0.664 P=0.686N |P=0.436 P=0.239 P=0.680N P=0.339 | |LOGISTIC REGRESSION| P=0.616N P=0.693 P=0.690 P=0.686N |P=0.486 P=0.223 P=0.611N P=0.359 | |COCH-ARM / FISHERS | P=0.622 P=0.691N P=0.691N P=0.691N |P=0.450 P=0.226 P=0.691N P=0.349 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |2/49 (4%) 2/50 (4%) 0/49 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 0/40.89 0/39.45 0/39.45 0/42.44 |2/44.01 2/45.74 0/44.51 2/44.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.5% 4.4% 0.0% 4.5% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 0/30 (0%) |2/33 (6%) 2/39 (5%) 0/35 (0%) 2/34 (6%) | |FIRST INCIDENCE | --- --- --- --- |730 (T) 730 (T) --- 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.602 P=0.634N P=0.225N P=0.685N | |POLY 3 | (e) (e) (e) (e) |P=0.612 P=0.680N P=0.235N P=0.694N | |POLY 1.5 | (e) (e) (e) (e) |P=0.615 P=0.683N P=0.237N P=0.691N | |POLY 6 | (e) (e) (e) (e) |P=0.607 P=0.674N P=0.231N P=0.691 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.602 P=0.634N (e) P=0.685N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.621 P=0.684N P=0.247N P=0.684N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 32 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 14/49 (29%) 23/47 (49%) 10/49 (20%) 13/49 (27%) |44/49 (90%) 44/50 (88%) 42/50 (84%) 42/50 (84%) | |POLY-3 RATE (b) | 14/42.09 23/40.45 10/39.80 13/42.47 |44/47.69 44/48.57 42/47.34 42/47.58 | |POLY-3 PERCENT (g) | 33.3% 56.9% 25.1% 30.6% |92.3% 90.6% 88.7% 88.3% | |TERMINAL (d) | 9/30 (30%) 9/21 (43%) 5/20 (25%) 8/30 (27%) |30/33 (91%) 36/39 (92%) 31/35 (89%) 30/34 (88%) | |FIRST INCIDENCE | 216 584 483 645 |544 572 617 590 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.105N P=0.010 * P=0.549N P=0.495N |P=0.532N P=0.166N P=0.267N P=0.387N | |POLY 3 | P=0.121N P=0.022 * P=0.284N P=0.489N |P=0.337N P=0.529N P=0.400N P=0.371N | |POLY 1.5 | P=0.127N P=0.028 * P=0.252N P=0.483N |P=0.303N P=0.527N P=0.366N P=0.337N | |POLY 6 | P=0.118N P=0.017 * P=0.347N P=0.501N |P=0.383N P=0.538N P=0.438N P=0.417N | |LOGISTIC REGRESSION| P=0.116N P=0.030 * P=0.249N P=0.466N |P=0.339N P=0.490N P=0.253N P=0.339N | |COCH-ARM / FISHERS | P=0.151N P=0.033 * P=0.241N P=0.500N |P=0.261N P=0.514N P=0.290N P=0.290N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Mesentery | | Accessory Spleen | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/8 (50%) 2/7 (29%) 2/13 (15%) 0/15 (0%) |0/1 (0%) 2/6 (33%) 0/1 (0%) 2/6 (33%) | |POLY-3 RATE (b) | 4/7.89 2/6.24 2/10.24 0/12.57 |0/0.90 2/5.66 0/0.98 2/5.61 | |POLY-3 PERCENT (g) | 50.7% 32.1% 19.5% 0.0% |0.0% 35.4% 0.0% 35.7% | |TERMINAL (d) | 0/3 (0%) 1/4 (25%) 0/4 (0%) 0/9 (0%) |0/0 (0%) 2/5 (40%) 0/0 (0%) 2/5 (40%) | |FIRST INCIDENCE | 528 725 510 --- |--- 730 (T) --- 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.044N* P=0.412N P=0.423N P=0.067N |P=0.677 P=1.000 (e) P=1.000 | |POLY 3 | P=0.005N** P=0.438N P=0.176N P=0.003N** |P=0.556 P=0.686 (e) P=0.685 | |POLY 1.5 | P=0.005N** P=0.412N P=0.144N P=0.002N** |P=0.554 P=0.679 (e) P=0.679 | |POLY 6 | P=0.005N** P=0.478N P=0.231N P=0.004N** |P=0.564 P=0.700 (e) P=0.699 | |LOGISTIC REGRESSION| P=0.007N** P=0.424N P=0.071N P=0.006N** |(e) P=1.000 (e) P=1.000 | |COCH-ARM / FISHERS | P=0.008N** P=0.378N P=0.115N P=0.008N** |P=0.560 P=0.714 (e) P=0.714 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 33 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/8 (63%) 6/7 (86%) 11/13 (85%) 12/15 (80%) |1/1 (100%) 4/6 (67%) 1/1 (100%) 5/6 (83%) | |POLY-3 RATE (b) | 5/6.88 6/6.98 11/12.24 12/14.93 |1/1.00 4/6.00 1/1.00 5/6.00 | |POLY-3 PERCENT (g) | 72.6% 85.9% 89.9% 80.4% |100.0% 66.7% 100.0% 83.3% | |TERMINAL (d) | 3/3 (100%) 4/4 (100%) 4/4 (100%) 7/9 (78%) |0/0 (0%) 3/5 (60%) 0/0 (0%) 4/5 (80%) | |FIRST INCIDENCE | 700 610 373 266 |704 634 725 618 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.428 P=0.623 P=0.063 P=0.386 |P=0.442 P=0.740N (e) P=0.754 | |POLY 3 | P=0.599N P=0.522 P=0.355 P=0.559 |P=0.530 P=0.673N (e) P=0.828N | |POLY 1.5 | P=0.587 P=0.431 P=0.303 P=0.459 |P=0.530 P=0.673N (e) P=0.828N | |POLY 6 | P=0.491N P=0.671 P=0.486 P=0.702 |P=0.530 P=0.673N (e) P=0.828N | |LOGISTIC REGRESSION| P=0.461 P=0.396 P=0.170 P=0.338 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.464 P=0.338 P=0.262 P=0.334 |P=0.534 P=0.714N (e) P=0.857N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Nose | | Foreign Body | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 3/50 (6%) 1/50 (2%) 2/50 (4%) |1/49 (2%) 0/50 (0%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 4/41.21 3/40.66 1/39.78 2/42.44 |1/44.60 0/45.74 1/45.30 2/44.02 | |POLY-3 PERCENT (g) | 9.7% 7.4% 2.5% 4.7% |2.2% 0.0% 2.2% 4.5% | |TERMINAL (d) | 2/30 (7%) 1/21 (5%) 0/21 (0%) 2/30 (7%) |0/33 (0%) 0/39 (0%) 1/35 (3%) 2/34 (6%) | |FIRST INCIDENCE | 646 506 638 729 (T) |544 --- 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.268N P=0.615N P=0.268N P=0.341N |P=0.227 P=0.492N P=0.754N P=0.509 | |POLY 3 | P=0.290N P=0.507N P=0.188N P=0.323N |P=0.229 P=0.495N P=0.757N P=0.495 | |POLY 1.5 | P=0.296N P=0.493N P=0.179N P=0.322N |P=0.233 P=0.496N P=0.758N P=0.500 | |POLY 6 | P=0.283N P=0.538N P=0.207N P=0.329N |P=0.223 P=0.493N P=0.756N P=0.490 | |LOGISTIC REGRESSION| P=0.301N P=0.500N P=0.187N P=0.323N |P=0.245 P=0.417N P=0.736N P=0.527 | |COCH-ARM / FISHERS | P=0.305N P=0.500N P=0.181N P=0.339N |P=0.238 P=0.495N P=0.747N P=0.508 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 34 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Nose | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 8/50 (16%) 9/50 (18%) 8/50 (16%) |6/49 (12%) 3/50 (6%) 5/50 (10%) 5/50 (10%) | |POLY-3 RATE (b) | 9/42.23 8/41.06 9/42.78 8/42.58 |6/44.72 3/46.26 5/45.91 5/44.02 | |POLY-3 PERCENT (g) | 21.3% 19.5% 21.0% 18.8% |13.4% 6.5% 10.9% 11.4% | |TERMINAL (d) | 5/30 (17%) 4/21 (19%) 1/21 (5%) 6/30 (20%) |3/33 (9%) 2/39 (5%) 3/35 (9%) 5/34 (15%) | |FIRST INCIDENCE | 406 506 533 711 |544 572 617 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.382N P=0.498 P=0.463 P=0.494N |P=0.518 P=0.192N P=0.466N P=0.489N | |POLY 3 | P=0.469N P=0.526N P=0.593N P=0.492N |P=0.525 P=0.225N P=0.482N P=0.511N | |POLY 1.5 | P=0.473N P=0.498N P=0.585N P=0.484N |P=0.538 P=0.229N P=0.487N P=0.501N | |POLY 6 | P=0.466N P=0.577N P=0.603 P=0.510N |P=0.506 P=0.218N P=0.471N P=0.524N | |LOGISTIC REGRESSION| P=0.481N P=0.499N P=0.598 P=0.470N |P=0.554 P=0.236N P=0.484N P=0.500N | |COCH-ARM / FISHERS | P=0.489N P=0.500N P=0.602N P=0.500N |P=0.557 P=0.233N P=0.486N P=0.486N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Nose: Respiratory Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 7/50 (14%) 8/50 (16%) 5/50 (10%) |6/49 (12%) 4/50 (8%) 4/50 (8%) 1/50 (2%) | |POLY-3 RATE (b) | 6/41.27 7/40.77 8/42.80 5/42.58 |6/45.06 4/45.74 4/45.70 1/44.29 | |POLY-3 PERCENT (g) | 14.5% 17.2% 18.7% 11.7% |13.3% 8.8% 8.8% 2.3% | |TERMINAL (d) | 4/30 (13%) 3/21 (14%) 0/21 (0%) 3/30 (10%) |3/33 (9%) 4/39 (10%) 3/35 (9%) 0/34 (0%) | |FIRST INCIDENCE | 646 506 533 711 |544 730 (T) 617 657 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.296N P=0.309 P=0.297 P=0.494N |P=0.064N P=0.296N P=0.346N P=0.064N | |POLY 3 | P=0.338N P=0.490 P=0.414 P=0.478N |P=0.058N P=0.360N P=0.360N P=0.058N | |POLY 1.5 | P=0.346N P=0.510 P=0.414 P=0.477N |P=0.056N P=0.360N P=0.362N P=0.056N | |POLY 6 | P=0.331N P=0.449 P=0.406 P=0.486N |P=0.061N P=0.358N P=0.357N P=0.061N | |LOGISTIC REGRESSION| P=0.365N P=0.485 P=0.383 P=0.481N |P=0.052N P=0.358N P=0.351N P=0.048N* | |COCH-ARM / FISHERS | P=0.370N P=0.500 P=0.387 P=0.500N |P=0.053N P=0.357N P=0.357N P=0.053N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 35 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Nose: Respiratory Epithelium | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 3/50 (6%) 5/50 (10%) 1/50 (2%) |1/49 (2%) 1/50 (2%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 4/41.84 3/39.50 5/41.23 1/42.51 |1/44.01 1/45.74 0/45.30 2/44.02 | |POLY-3 PERCENT (g) | 9.6% 7.6% 12.1% 2.4% |2.3% 2.2% 0.0% 4.5% | |TERMINAL (d) | 1/30 (3%) 2/21 (10%) 1/21 (5%) 0/30 (0%) |1/33 (3%) 1/39 (3%) 0/35 (0%) 2/34 (6%) | |FIRST INCIDENCE | 406 716 533 711 |730 (T) 730 (T) --- 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.137N P=0.641N P=0.409 P=0.183N |P=0.317 P=0.724N P=0.488N P=0.510 | |POLY 3 | P=0.138N P=0.532N P=0.491 P=0.173N |P=0.329 P=0.752N P=0.494N P=0.500 | |POLY 1.5 | P=0.145N P=0.508N P=0.504 P=0.172N |P=0.332 P=0.754N P=0.496N P=0.503 | |POLY 6 | P=0.131N P=0.571N P=0.467 P=0.176N |P=0.324 P=0.748N P=0.491N P=0.497 | |LOGISTIC REGRESSION| P=0.161N P=0.501N P=0.484 P=0.185N |P=0.317 P=0.724N (e) P=0.510 | |COCH-ARM / FISHERS | P=0.157N P=0.500N P=0.500 P=0.181N |P=0.335 P=0.747N P=0.495N P=0.508 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |10/49 (20%) 6/50 (12%) 6/50 (12%) 7/50 (14%) | |POLY-3 RATE (b) | |10/45.60 6/45.74 6/46.54 7/44.51 | |POLY-3 PERCENT (g) | |21.9% 13.1% 12.9% 15.7% | |TERMINAL (d) | |5/33 (15%) 6/39 (15%) 3/35 (9%) 5/34 (15%) | |FIRST INCIDENCE | |497 730 (T) 232 603 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.445N P=0.146N P=0.193N P=0.304N | |POLY 3 | |P=0.422N P=0.202N P=0.192N P=0.315N | |POLY 1.5 | |P=0.410N P=0.200N P=0.193N P=0.302N | |POLY 6 | |P=0.437N P=0.204N P=0.191N P=0.332N | |LOGISTIC REGRESSION| |P=0.378N P=0.195N P=0.174N P=0.277N | |COCH-ARM / FISHERS | |P=0.393N P=0.194N P=0.194N P=0.282N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 36 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Pancreas | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 23/50 (46%) 19/50 (38%) 16/50 (32%) 23/50 (46%) |13/49 (27%) 15/50 (30%) 18/49 (37%) 13/50 (26%) | |POLY-3 RATE (b) | 23/43.83 19/41.67 16/41.97 23/44.93 |13/44.62 15/47.10 18/45.86 13/44.68 | |POLY-3 PERCENT (g) | 52.5% 45.6% 38.1% 51.2% |29.1% 31.9% 39.3% 29.1% | |TERMINAL (d) | 17/30 (57%) 10/21 (48%) 9/21 (43%) 16/30 (53%) |11/33 (33%) 11/39 (28%) 12/35 (34%) 11/34 (32%) | |FIRST INCIDENCE | 406 584 550 590 |544 572 592 597 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.486N P=0.453 P=0.410N P=0.551N |P=0.507N P=0.580N P=0.262 P=0.562N | |POLY 3 | P=0.458 P=0.333N P=0.125N P=0.537N |P=0.484N P=0.478 P=0.213 P=0.591N | |POLY 1.5 | P=0.426 P=0.279N P=0.105N P=0.535N |P=0.463N P=0.457 P=0.197 P=0.583N | |POLY 6 | P=0.503 P=0.425N P=0.165N P=0.542N |P=0.510N P=0.513 P=0.244 P=0.590 | |LOGISTIC REGRESSION| P=0.454 P=0.291N P=0.112N P=0.523N |P=0.464N P=0.448 P=0.198 P=0.585 | |COCH-ARM / FISHERS | P=0.374 P=0.272N P=0.109N P=0.579N |P=0.433N P=0.437 P=0.193 P=0.567N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 0/50 (0%) 1/48 (2%) 1/50 (2%) |9/49 (18%) 10/50 (20%) 6/49 (12%) 5/49 (10%) | |POLY-3 RATE (b) | 1/39.89 0/39.45 1/38.39 1/42.44 |9/44.68 10/45.74 6/44.59 5/43.29 | |POLY-3 PERCENT (g) | 2.5% 0.0% 2.6% 2.4% |20.1% 21.9% 13.5% 11.6% | |TERMINAL (d) | 1/29 (3%) 0/21 (0%) 0/20 (0%) 1/30 (3%) |7/33 (21%) 10/39 (26%) 5/35 (14%) 4/33 (12%) | |FIRST INCIDENCE | 729 (T) --- 624 729 (T) |630 730 (T) 711 657 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.585 P=0.564N P=0.720 P=0.755N |P=0.140N P=0.559N P=0.249N P=0.199N | |POLY 3 | P=0.576 P=0.502N P=0.753 P=0.747N |P=0.127N P=0.523 P=0.287N P=0.209N | |POLY 1.5 | P=0.567 P=0.495N P=0.758 P=0.748N |P=0.122N P=0.520 P=0.291N P=0.203N | |POLY 6 | P=0.588 P=0.515N P=0.742 P=0.749N |P=0.134N P=0.528 P=0.281N P=0.217N | |LOGISTIC REGRESSION| P=0.568 (e) P=0.758 P=0.755N |P=0.135N P=0.555 P=0.272N P=0.206N | |COCH-ARM / FISHERS | P=0.554 P=0.495N P=0.747 P=0.747N |P=0.115N P=0.520 P=0.288N P=0.194N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 37 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/49 (14%) 9/50 (18%) 5/48 (10%) 3/50 (6%) |22/49 (45%) 11/50 (22%) 13/49 (27%) 16/49 (33%) | |POLY-3 RATE (b) | 7/40.81 9/41.23 5/39.12 3/42.55 |22/45.25 11/46.05 13/46.82 16/44.46 | |POLY-3 PERCENT (g) | 17.2% 21.8% 12.8% 7.1% |48.6% 23.9% 27.8% 36.0% | |TERMINAL (d) | 4/29 (14%) 3/21 (14%) 1/20 (5%) 2/30 (7%) |16/33 (49%) 10/39 (26%) 9/35 (26%) 12/33 (36%) | |FIRST INCIDENCE | 406 561 605 700 |610 646 232 590 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.054N P=0.238 P=0.552N P=0.154N |P=0.515N P=0.006N** P=0.041N* P=0.170N | |POLY 3 | P=0.054N P=0.399 P=0.408N P=0.138N |P=0.457N P=0.010N* P=0.029N* P=0.156N | |POLY 1.5 | P=0.057N P=0.418 P=0.391N P=0.138N |P=0.448N P=0.011N* P=0.035N* P=0.154N | |POLY 6 | P=0.052N P=0.366 P=0.436N P=0.141N |P=0.469N P=0.009N** P=0.025N* P=0.160N | |LOGISTIC REGRESSION| P=0.059N P=0.410 P=0.393N P=0.138N |P=0.442N P=0.010N* P=0.045N* P=0.168N | |COCH-ARM / FISHERS | P=0.065N P=0.410 P=0.394N P=0.151N |P=0.434N P=0.013N* P=0.046N* P=0.150N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/49 (12%) 3/50 (6%) 5/48 (10%) 1/50 (2%) |13/49 (27%) 10/50 (20%) 3/49 (6%) 5/49 (10%) | |POLY-3 RATE (b) | 6/40.55 3/40.00 5/38.76 1/42.44 |13/45.15 10/45.74 3/44.52 5/43.02 | |POLY-3 PERCENT (g) | 14.8% 7.5% 12.9% 2.4% |28.8% 21.9% 6.7% 11.6% | |TERMINAL (d) | 3/29 (10%) 2/21 (10%) 3/20 (15%) 1/30 (3%) |10/33 (30%) 10/39 (26%) 3/35 (9%) 5/33 (15%) | |FIRST INCIDENCE | 590 557 602 729 (T) |527 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.057N P=0.380N P=0.573 P=0.057N |P=0.038N* P=0.187N P=0.005N** P=0.035N* | |POLY 3 | P=0.059N P=0.246N P=0.532N P=0.048N* |P=0.033N* P=0.302N P=0.006N** P=0.039N* | |POLY 1.5 | P=0.064N P=0.230N P=0.512N P=0.048N* |P=0.031N* P=0.302N P=0.006N** P=0.036N* | |POLY 6 | P=0.054N P=0.280N P=0.571N P=0.050N |P=0.036N* P=0.299N P=0.005N** P=0.043N* | |LOGISTIC REGRESSION| P=0.064N P=0.240N P=0.530N P=0.049N* |P=0.036N* P=0.276N P=0.007N** P=0.037N* | |COCH-ARM / FISHERS | P=0.072N P=0.233N P=0.515N P=0.053N |P=0.031N* P=0.298N P=0.006N** P=0.033N* | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 38 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 17/50 (34%) 20/50 (40%) 13/50 (26%) 20/50 (40%) | | |POLY-3 RATE (b) | 17/43.04 20/42.86 13/42.91 20/44.92 | | |POLY-3 PERCENT (g) | 39.5% 46.7% 30.3% 44.5% | | |TERMINAL (d) | 12/30 (40%) 10/21 (48%) 5/21 (24%) 12/30 (40%) | | |FIRST INCIDENCE | 122 464 368 539 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.537N P=0.101 P=0.548N P=0.370 | | |POLY 3 | P=0.423 P=0.322 P=0.249N P=0.396 | | |POLY 1.5 | P=0.396 P=0.346 P=0.237N P=0.380 | | |POLY 6 | P=0.459 P=0.278 P=0.289N P=0.408 | | |LOGISTIC REGRESSION| P=0.377 P=0.340 P=0.258N P=0.368 | | |COCH-ARM / FISHERS | P=0.358 P=0.339 P=0.257N P=0.339 | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Prostate | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 5/50 (10%) 4/50 (8%) 6/50 (12%) | | |POLY-3 RATE (b) | 5/41.30 5/40.59 4/39.55 6/42.51 | | |POLY-3 PERCENT (g) | 12.1% 12.3% 10.1% 14.1% | | |TERMINAL (d) | 3/30 (10%) 3/21 (14%) 3/21 (14%) 5/30 (17%) | | |FIRST INCIDENCE | 617 511 704 711 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.522 P=0.467 P=0.588 P=0.503 | | |POLY 3 | P=0.448 P=0.621 P=0.527N P=0.520 | | |POLY 1.5 | P=0.440 P=0.624N P=0.504N P=0.522 | | |POLY 6 | P=0.456 P=0.585 P=0.569N P=0.511 | | |LOGISTIC REGRESSION| P=0.468 P=0.627 P=0.580N P=0.518 | | |COCH-ARM / FISHERS | P=0.420 P=0.630N P=0.500N P=0.500 | | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 39 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Prostate | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 26/50 (52%) 24/50 (48%) 28/50 (56%) 29/50 (58%) | | |POLY-3 RATE (b) | 26/45.50 24/44.58 28/46.88 29/48.61 | | |POLY-3 PERCENT (g) | 57.1% 53.8% 59.7% 59.7% | | |TERMINAL (d) | 15/30 (50%) 9/21 (43%) 8/21 (38%) 15/30 (50%) | | |FIRST INCIDENCE | 122 491 368 266 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.483 P=0.336 P=0.169 P=0.406 | | |POLY 3 | P=0.386 P=0.458N P=0.483 P=0.485 | | |POLY 1.5 | P=0.328 P=0.422N P=0.479 P=0.446 | | |POLY 6 | P=0.451 P=0.521N P=0.469 P=0.514 | | |LOGISTIC REGRESSION| P=0.195 P=0.420N P=0.417 P=0.313 | | |COCH-ARM / FISHERS | P=0.230 P=0.421N P=0.421 P=0.344 | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Prostate: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 12/50 (24%) 3/50 (6%) 10/50 (20%) 9/50 (18%) | | |POLY-3 RATE (b) | 12/41.52 3/39.60 10/41.10 9/43.28 | | |POLY-3 PERCENT (g) | 28.9% 7.6% 24.3% 20.8% | | |TERMINAL (d) | 10/30 (33%) 2/21 (10%) 4/21 (19%) 6/30 (20%) | | |FIRST INCIDENCE | 604 690 617 605 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.500N P=0.051N P=0.509 P=0.304N | | |POLY 3 | P=0.566N P=0.012N* P=0.412N P=0.269N | | |POLY 1.5 | P=0.536 P=0.010N* P=0.392N P=0.275N | | |POLY 6 | P=0.521N P=0.017N* P=0.451N P=0.270N | | |LOGISTIC REGRESSION| P=0.556 P=0.021N* P=0.456N P=0.278N | | |COCH-ARM / FISHERS | P=0.491 P=0.011N* P=0.405N P=0.312N | | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 40 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Salivary Glands | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |1/49 (2%) 0/50 (0%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | 0/40.89 0/39.45 0/39.45 0/41.51 |1/44.01 0/45.74 1/45.32 2/44.32 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.3% 0.0% 2.2% 4.5% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 0/30 (0%) |1/33 (3%) 0/39 (0%) 0/35 (0%) 1/34 (3%) | |FIRST INCIDENCE | --- --- --- --- |730 (T) --- 725 646 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.222 P=0.467N P=0.748N P=0.507 | |POLY 3 | (e) (e) (e) (e) |P=0.232 P=0.492N P=0.754N P=0.502 | |POLY 1.5 | (e) (e) (e) (e) |P=0.235 P=0.494N P=0.756N P=0.504 | |POLY 6 | (e) (e) (e) (e) |P=0.228 P=0.489N P=0.751N P=0.501 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.233 (e) P=0.750N P=0.504 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.238 P=0.495N P=0.747N P=0.508 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Skin | | Cyst Epithelial Inclusion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 3/49 (6%) 2/49 (4%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/40.89 0/39.45 3/39.03 2/41.47 |0/44.01 0/45.74 0/45.30 0/44.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 7.7% 4.8% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 1/29 (3%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- 689 720 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.202 (e) P=0.082 P=0.236 |(e) (e) (e) (e) | |POLY 3 | P=0.169 (e) P=0.110 P=0.240 |(e) (e) (e) (e) | |POLY 1.5 | P=0.164 (e) P=0.115 P=0.240 |(e) (e) (e) (e) | |POLY 6 | P=0.174 (e) P=0.101 P=0.238 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.177 (e) P=0.102 P=0.233 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.154 (e) P=0.117 P=0.242 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 41 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Skin | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 1/49 (2%) 0/49 (0%) |1/49 (2%) 1/50 (2%) 1/50 (2%) 3/50 (6%) | |POLY-3 RATE (b) | 2/41.09 3/39.53 1/39.06 0/41.44 |1/44.01 1/45.74 1/45.30 3/44.02 | |POLY-3 PERCENT (g) | 4.9% 7.6% 2.6% 0.0% |2.3% 2.2% 2.2% 6.8% | |TERMINAL (d) | 1/30 (3%) 1/21 (5%) 0/21 (0%) 0/29 (0%) |1/33 (3%) 1/39 (3%) 1/35 (3%) 3/34 (9%) | |FIRST INCIDENCE | 679 714 644 --- |730 (T) 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.103N P=0.368 P=0.575N P=0.247N |P=0.143 P=0.724N P=0.749N P=0.315 | |POLY 3 | P=0.103N P=0.482 P=0.518N P=0.235N |P=0.153 P=0.752N P=0.754N P=0.305 | |POLY 1.5 | P=0.104N P=0.499 P=0.507N P=0.235N |P=0.156 P=0.754N P=0.756N P=0.308 | |POLY 6 | P=0.102N P=0.451 P=0.537N P=0.238N |P=0.149 P=0.748N P=0.751N P=0.302 | |LOGISTIC REGRESSION| P=0.103N P=0.432 P=0.511N P=0.235N |P=0.143 P=0.724N P=0.749N P=0.315 | |COCH-ARM / FISHERS | P=0.110N P=0.500 P=0.508N P=0.253N |P=0.159 P=0.747N P=0.747N P=0.316 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Skin | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 0/49 (0%) 1/49 (2%) |1/49 (2%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 2/41.09 2/39.62 0/38.75 1/42.20 |1/44.01 0/45.74 1/45.30 0/44.02 | |POLY-3 PERCENT (g) | 4.9% 5.1% 0.0% 2.4% |2.3% 0.0% 2.2% 0.0% | |TERMINAL (d) | 1/30 (3%) 0/21 (0%) 0/21 (0%) 0/29 (0%) |1/33 (3%) 0/39 (0%) 1/35 (3%) 0/34 (0%) | |FIRST INCIDENCE | 679 690 --- 449 |730 (T) --- 730 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.363N P=0.590 P=0.304N P=0.500N |P=0.468N P=0.467N P=0.749N P=0.494N | |POLY 3 | P=0.378N P=0.682 P=0.250N P=0.491N |P=0.464N P=0.492N P=0.754N P=0.500N | |POLY 1.5 | P=0.384N P=0.694 P=0.242N P=0.492N |P=0.461N P=0.494N P=0.756N P=0.499N | |POLY 6 | P=0.372N P=0.658 P=0.264N P=0.493N |P=0.469N P=0.489N P=0.751N P=0.502N | |LOGISTIC REGRESSION| P=0.400N P=0.666 P=0.255N P=0.540N |P=0.468N (e) P=0.749N (e) | |COCH-ARM / FISHERS | P=0.393N P=0.691N P=0.253N P=0.508N |P=0.457N P=0.495N P=0.747N P=0.495N | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 42 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Skin | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/49 (0%) 0/49 (0%) |2/49 (4%) 1/50 (2%) 4/50 (8%) 3/50 (6%) | |POLY-3 RATE (b) | 0/40.89 2/40.01 0/38.75 0/41.44 |2/44.01 1/45.74 4/45.30 3/44.64 | |POLY-3 PERCENT (g) | 0.0% 5.0% 0.0% 0.0% |4.5% 2.2% 8.8% 6.7% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 0/29 (0%) |2/33 (6%) 1/39 (3%) 4/35 (11%) 2/34 (6%) | |FIRST INCIDENCE | --- 610 --- --- |730 (T) 730 (T) 730 (T) 529 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.367N P=0.217 (e) (e) |P=0.320 P=0.442N P=0.363 P=0.515 | |POLY 3 | P=0.382N P=0.232 (e) (e) |P=0.336 P=0.487N P=0.350 P=0.506 | |POLY 1.5 | P=0.379N P=0.239 (e) (e) |P=0.340 P=0.490N P=0.347 P=0.507 | |POLY 6 | P=0.391N P=0.220 (e) (e) |P=0.329 P=0.481N P=0.357 P=0.506 | |LOGISTIC REGRESSION| P=0.391N P=0.235 (e) (e) |P=0.333 P=0.442N P=0.363 P=0.514 | |COCH-ARM / FISHERS | P=0.386N P=0.247 (e) (e) |P=0.345 P=0.492N P=0.349 P=0.510 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Skin: Epidermis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 0/49 (0%) 0/49 (0%) |4/49 (8%) 2/50 (4%) 5/50 (10%) 5/50 (10%) | |POLY-3 RATE (b) | 1/40.89 3/39.62 0/38.75 0/41.44 |4/44.01 2/45.74 5/45.30 5/44.64 | |POLY-3 PERCENT (g) | 2.5% 7.6% 0.0% 0.0% |9.1% 4.4% 11.0% 11.2% | |TERMINAL (d) | 1/30 (3%) 1/21 (5%) 0/21 (0%) 0/29 (0%) |4/33 (12%) 2/39 (5%) 5/35 (14%) 4/34 (12%) | |FIRST INCIDENCE | 729 (T) 690 --- --- |730 (T) 730 (T) 730 (T) 529 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.149N P=0.202 P=0.571N P=0.507N |P=0.276 P=0.262N P=0.537 P=0.520 | |POLY 3 | P=0.154N P=0.293 P=0.511N P=0.497N |P=0.298 P=0.319N P=0.518 P=0.509 | |POLY 1.5 | P=0.153N P=0.306 P=0.504N P=0.497N |P=0.303 P=0.324N P=0.513 P=0.510 | |POLY 6 | P=0.157N P=0.271 P=0.522N P=0.499N |P=0.290 P=0.311N P=0.527 P=0.508 | |LOGISTIC REGRESSION| P=0.150N P=0.242 (e) (e) |P=0.283 P=0.262N P=0.537 P=0.503 | |COCH-ARM / FISHERS | P=0.160N P=0.309 P=0.505N P=0.505N |P=0.308 P=0.329N P=0.513 P=0.513 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 43 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Spleen | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 8/50 (16%) 9/50 (18%) 3/50 (6%) 3/50 (6%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) | |POLY-3 RATE (b) | 8/40.89 9/40.67 3/39.98 3/43.03 |0/44.24 0/45.74 0/45.30 2/44.45 | |POLY-3 PERCENT (g) | 19.6% 22.1% 7.5% 7.0% |0.0% 0.0% 0.0% 4.5% | |TERMINAL (d) | 8/30 (27%) 5/21 (24%) 1/21 (5%) 2/30 (7%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 1/34 (3%) | |FIRST INCIDENCE | 729 (T) 610 603 539 |--- --- --- 603 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.032N* P=0.253 P=0.226N P=0.095N |P=0.039 * (e) (e) P=0.241 | |POLY 3 | P=0.032N* P=0.495 P=0.102N P=0.081N |P=0.040 * (e) (e) P=0.238 | |POLY 1.5 | P=0.036N* P=0.514 P=0.095N P=0.084N |P=0.041 * (e) (e) P=0.238 | |POLY 6 | P=0.029N* P=0.458 P=0.117N P=0.079N |P=0.040 * (e) (e) P=0.238 | |LOGISTIC REGRESSION| P=0.036N* P=0.408 P=0.143N P=0.089N |P=0.043 * (e) (e) P=0.240 | |COCH-ARM / FISHERS | P=0.045N* P=0.500 P=0.100N P=0.100N |P=0.042 * (e) (e) P=0.247 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 5/50 (10%) 4/50 (8%) 8/50 (16%) |27/50 (54%) 24/50 (48%) 31/50 (62%) 40/50 (80%) | |POLY-3 RATE (b) | 3/43.19 5/40.68 4/40.74 8/43.30 |27/47.19 24/47.08 31/47.89 40/48.43 | |POLY-3 PERCENT (g) | 7.0% 12.3% 9.8% 18.5% |57.2% 51.0% 64.7% 82.6% | |TERMINAL (d) | 0/30 (0%) 2/21 (10%) 0/21 (0%) 5/30 (17%) |18/33 (55%) 21/39 (54%) 23/35 (66%) 29/34 (85%) | |FIRST INCIDENCE | 122 464 603 617 |497 396 232 360 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.128 P=0.299 P=0.484 P=0.116 |P<0.001 ** P=0.157N P=0.406 P=0.026 * | |POLY 3 | P=0.082 P=0.323 P=0.468 P=0.097 |P<0.001 ** P=0.342N P=0.291 P=0.004 ** | |POLY 1.5 | P=0.080 P=0.343 P=0.486 P=0.100 |P<0.001 ** P=0.340N P=0.285 P=0.004 ** | |POLY 6 | P=0.084 P=0.290 P=0.441 P=0.094 |P<0.001 ** P=0.354N P=0.296 P=0.004 ** | |LOGISTIC REGRESSION| P=0.054 P=0.221 P=0.364 P=0.064 |P<0.001 ** P=0.327N P=0.274 P=0.005 ** | |COCH-ARM / FISHERS | P=0.078 P=0.357 P=0.500 P=0.100 |P<0.001 ** P=0.345N P=0.272 P=0.005 ** | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 44 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Spleen | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 1/50 (2%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 1/41.06 1/39.60 2/40.41 1/42.51 |1/44.41 1/46.19 0/45.30 0/44.02 | |POLY-3 PERCENT (g) | 2.4% 2.5% 5.0% 2.4% |2.3% 2.2% 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/21 (0%) 0/30 (0%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 686 690 373 711 |686 600 --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.597N P=0.705 P=0.451 P=0.757N |P=0.313N P=0.747N P=0.495N P=0.505N | |POLY 3 | P=0.620N P=0.753 P=0.494 P=0.753N |P=0.309N P=0.752N P=0.496N P=0.502N | |POLY 1.5 | P=0.626N P=0.761 P=0.504 P=0.753N |P=0.308N P=0.756N P=0.498N P=0.501N | |POLY 6 | P=0.614N P=0.738 P=0.475 P=0.756N |P=0.311N P=0.747N P=0.493N P=0.503N | |LOGISTIC REGRESSION| P=0.644 P=0.759 P=0.462 P=0.756N |P=0.297N P=0.749 P=0.500N P=0.499N | |COCH-ARM / FISHERS | P=0.639N P=0.753N P=0.500 P=0.753N |P=0.306N P=0.753N P=0.500N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 4/50 (8%) 4/50 (8%) |30/50 (60%) 30/50 (60%) 35/50 (70%) 43/50 (86%) | |POLY-3 RATE (b) | 1/40.89 2/40.19 4/40.66 4/43.17 |30/46.81 30/46.75 35/46.35 43/47.35 | |POLY-3 PERCENT (g) | 2.5% 5.0% 9.8% 9.3% |64.1% 64.2% 75.5% 90.8% | |TERMINAL (d) | 1/30 (3%) 1/21 (5%) 1/21 (5%) 2/30 (7%) |23/33 (70%) 26/39 (67%) 29/35 (83%) 33/34 (97%) | |FIRST INCIDENCE | 729 (T) 462 483 607 |497 572 648 529 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.212 P=0.427 P=0.135 P=0.189 |P<0.001 ** P=0.254N P=0.341 P=0.014 * | |POLY 3 | P=0.184 P=0.494 P=0.176 P=0.195 |P<0.001 ** P=0.584 P=0.155 P<0.001 ** | |POLY 1.5 | P=0.176 P=0.504 P=0.182 P=0.192 |P<0.001 ** P=0.580 P=0.165 P<0.001 ** | |POLY 6 | P=0.195 P=0.474 P=0.162 P=0.196 |P<0.001 ** P=0.586N P=0.150 P<0.001 ** | |LOGISTIC REGRESSION| P=0.147 P=0.492 P=0.178 P=0.186 |P<0.001 ** P=0.510N P=0.243 P=0.002 ** | |COCH-ARM / FISHERS | P=0.159 P=0.500 P=0.181 P=0.181 |P<0.001 ** P=0.581N P=0.201 P=0.003 ** | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 45 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Stomach, Forestomach | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 3/50 (6%) 2/49 (4%) 5/48 (10%) |1/49 (2%) 1/50 (2%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 4/42.59 3/40.07 2/39.67 5/41.61 |1/44.37 1/46.05 1/46.27 0/44.02 | |POLY-3 PERCENT (g) | 9.4% 7.5% 5.0% 12.0% |2.3% 2.2% 2.2% 0.0% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/20 (0%) 1/29 (3%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 284 638 368 597 |630 646 232 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.386 P=0.572N P=0.366N P=0.516 |P=0.331N P=0.755N P=0.758N P=0.514N | |POLY 3 | P=0.331 P=0.533N P=0.370N P=0.485 |P=0.330N P=0.752N P=0.751N P=0.502N | |POLY 1.5 | P=0.322 P=0.510N P=0.352N P=0.487 |P=0.327N P=0.754N P=0.753N P=0.499N | |POLY 6 | P=0.344 P=0.571N P=0.403N P=0.480 |P=0.335N P=0.749N P=0.749N P=0.505N | |LOGISTIC REGRESSION| P=0.254 P=0.540N P=0.432N P=0.424 |P=0.236N P=0.753N P=0.591N P=0.460N | |COCH-ARM / FISHERS | P=0.307 P=0.500N P=0.349N P=0.474 |P=0.321N P=0.747N P=0.747N P=0.495N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/50 (12%) 2/50 (4%) 4/49 (8%) 4/48 (8%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 6/43.28 2/39.97 4/39.48 4/41.49 |0/44.01 0/45.74 0/45.30 0/44.02 | |POLY-3 PERCENT (g) | 13.9% 5.0% 10.1% 9.6% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/20 (0%) 0/29 (0%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 284 638 603 597 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.473N P=0.190N P=0.439N P=0.362N |(e) (e) (e) (e) | |POLY 3 | P=0.525N P=0.158N P=0.428N P=0.396N |(e) (e) (e) (e) | |POLY 1.5 | P=0.539N P=0.142N P=0.400N P=0.390N |(e) (e) (e) (e) | |POLY 6 | P=0.506N P=0.188N P=0.472N P=0.406N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.583 P=0.159N P=0.409N P=0.455N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.557N P=0.134N P=0.383N P=0.397N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 46 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 4/50 (8%) 7/49 (14%) 5/48 (10%) |1/49 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 5/42.17 4/40.84 7/40.77 5/41.00 |1/44.70 0/45.74 0/45.30 0/44.02 | |POLY-3 PERCENT (g) | 11.9% 9.8% 17.2% 12.2% |2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/30 (3%) 1/21 (5%) 0/20 (0%) 2/29 (7%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 528 464 550 634 |497 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.549N P=0.594N P=0.312 P=0.623N |P=0.472N P=0.500N P=0.500N P=0.500N | |POLY 3 | P=0.526 P=0.520N P=0.354 P=0.613 |P=0.470N P=0.495N P=0.497N P=0.503N | |POLY 1.5 | P=0.520 P=0.499N P=0.370 P=0.618 |P=0.470N P=0.496N P=0.498N P=0.500N | |POLY 6 | P=0.533 P=0.560N P=0.327 P=0.602 |P=0.471N P=0.493N P=0.496N P=0.506N | |LOGISTIC REGRESSION| P=0.483 P=0.517N P=0.357 P=0.613 |P=0.431N P=0.353N P=0.346N P=0.316N | |COCH-ARM / FISHERS | P=0.502 P=0.500N P=0.365 P=0.603 |P=0.470N P=0.495N P=0.495N P=0.495N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Stomach, Glandular | | Edema | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 0/49 (0%) 0/48 (0%) |0/49 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 1/41.01 3/39.79 0/38.45 0/40.55 |0/44.01 0/45.74 1/46.27 0/44.02 | |POLY-3 PERCENT (g) | 2.4% 7.5% 0.0% 0.0% |0.0% 0.0% 2.2% 0.0% | |TERMINAL (d) | 0/30 (0%) 1/21 (5%) 0/20 (0%) 0/29 (0%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 700 679 --- --- |--- --- 232 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.151N P=0.222 P=0.546N P=0.500N |P=0.784N (e) P=0.500 (e) | |POLY 3 | P=0.157N P=0.294 P=0.513N P=0.502N |P=0.787N (e) P=0.510 (e) | |POLY 1.5 | P=0.157N P=0.306 P=0.505N P=0.502N |P=0.785N (e) P=0.507 (e) | |POLY 6 | P=0.160N P=0.272 P=0.527N P=0.505N |P=0.790N (e) P=0.513 (e) | |LOGISTIC REGRESSION| P=0.156N P=0.284 P=0.517N P=0.503N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.163N P=0.309 P=0.505N P=0.510N |P=0.783N (e) P=0.505 (e) | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 47 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Stomach, Glandular | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 2/50 (4%) 3/49 (6%) 1/48 (2%) |0/49 (0%) 1/50 (2%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 1/41.72 2/39.86 3/39.11 1/40.97 |0/44.01 1/46.12 1/45.32 1/44.29 | |POLY-3 PERCENT (g) | 2.4% 5.0% 7.7% 2.4% |0.0% 2.2% 2.2% 2.3% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/20 (0%) 0/29 (0%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 406 630 603 607 |--- 624 725 657 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.476N P=0.478 P=0.274 P=0.747N |P=0.469 P=0.504 P=0.511 P=0.505 | |POLY 3 | P=0.510N P=0.484 P=0.282 P=0.757 |P=0.480 P=0.509 P=0.506 P=0.501 | |POLY 1.5 | P=0.514N P=0.497 P=0.294 P=0.757 |P=0.482 P=0.507 P=0.504 P=0.502 | |POLY 6 | P=0.505N P=0.463 P=0.262 P=0.756 |P=0.477 P=0.514 P=0.509 P=0.501 | |LOGISTIC REGRESSION| P=0.563N P=0.445 P=0.270 P=0.680 |P=0.500 P=0.521 P=0.511 P=0.522 | |COCH-ARM / FISHERS | P=0.528N P=0.500 P=0.301 P=0.742 |P=0.487 P=0.505 P=0.505 P=0.505 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Stomach, Glandular | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 3/50 (6%) 1/49 (2%) 1/48 (2%) |0/49 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 2/41.03 3/39.86 1/38.75 1/40.66 |0/44.01 0/45.74 0/45.30 0/44.02 | |POLY-3 PERCENT (g) | 4.9% 7.5% 2.6% 2.5% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/30 (0%) 0/21 (0%) 0/20 (0%) 0/29 (0%) |0/33 (0%) 0/39 (0%) 0/35 (0%) 0/34 (0%) | |FIRST INCIDENCE | 700 636 645 702 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.274N P=0.385 P=0.579N P=0.500N |(e) (e) (e) (e) | |POLY 3 | P=0.302N P=0.487 P=0.520N P=0.503N |(e) (e) (e) (e) | |POLY 1.5 | P=0.306N P=0.502 P=0.508N P=0.503N |(e) (e) (e) (e) | |POLY 6 | P=0.299N P=0.460 P=0.541N P=0.507N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.301N P=0.474 P=0.517N P=0.505N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.316N P=0.500 P=0.508N P=0.515N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 48 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Testes: Germinal Epithelium | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 12/50 (24%) 3/50 (6%) 8/50 (16%) | | |POLY-3 RATE (b) | 7/43.00 12/43.46 3/39.90 8/43.03 | | |POLY-3 PERCENT (g) | 16.3% 27.6% 7.5% 18.6% | | |TERMINAL (d) | 2/30 (7%) 3/21 (14%) 1/21 (5%) 7/30 (23%) | | |FIRST INCIDENCE | 406 462 603 539 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.384N P=0.109 P=0.252N P=0.514 | | |POLY 3 | P=0.463N P=0.154 P=0.187N P=0.501 | | |POLY 1.5 | P=0.458N P=0.165 P=0.167N P=0.512 | | |POLY 6 | P=0.477N P=0.132 P=0.224N P=0.478 | | |LOGISTIC REGRESSION| P=0.493N P=0.130 P=0.161N P=0.501 | | |COCH-ARM / FISHERS | P=0.468N P=0.154 P=0.159N P=0.500 | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Testes: Interstitial Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 4/50 (8%) 8/50 (16%) 3/50 (6%) 5/50 (10%) | | |POLY-3 RATE (b) | 4/42.02 8/42.52 3/40.29 5/43.37 | | |POLY-3 PERCENT (g) | 9.5% 18.8% 7.5% 11.5% | | |TERMINAL (d) | 2/30 (7%) 2/21 (10%) 0/21 (0%) 2/30 (7%) | | |FIRST INCIDENCE | 472 464 603 602 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.435N P=0.139 P=0.569N P=0.521 | | |POLY 3 | P=0.477N P=0.180 P=0.523N P=0.520 | | |POLY 1.5 | P=0.482N P=0.189 P=0.504N P=0.520 | | |POLY 6 | P=0.473N P=0.161 P=0.555N P=0.517 | | |LOGISTIC REGRESSION| P=0.547N P=0.146 P=0.507N P=0.488 | | |COCH-ARM / FISHERS | P=0.501N P=0.178 P=0.500N P=0.500 | | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 49 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 7/50 (14%) 2/50 (4%) 7/50 (14%) 4/50 (8%) |21/49 (43%) 9/50 (18%) 11/50 (22%) 12/50 (24%) | |POLY-3 RATE (b) | 7/42.02 2/39.69 7/40.17 4/42.54 |21/44.65 9/46.26 11/45.40 12/45.09 | |POLY-3 PERCENT (g) | 16.7% 5.0% 17.4% 9.4% |47.0% 19.5% 24.2% 26.6% | |TERMINAL (d) | 5/30 (17%) 1/21 (5%) 5/21 (24%) 3/30 (10%) |17/33 (52%) 8/39 (21%) 9/35 (26%) 9/34 (27%) | |FIRST INCIDENCE | 472 665 609 702 |610 572 711 590 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.334N P=0.157N P=0.411 P=0.258N |P=0.229N P=0.002N** P=0.018N* P=0.042N* | |POLY 3 | P=0.379N P=0.091N P=0.580 P=0.252N |P=0.184N P=0.004N** P=0.018N* P=0.033N* | |POLY 1.5 | P=0.395N P=0.081N P=0.607 P=0.248N |P=0.180N P=0.004N** P=0.020N* P=0.035N* | |POLY 6 | P=0.358N P=0.111N P=0.532 P=0.261N |P=0.190N P=0.003N** P=0.015N* P=0.032N* | |LOGISTIC REGRESSION| P=0.381N P=0.082N P=0.601 P=0.244N |P=0.209N P=0.004N** P=0.014N* P=0.042N* | |COCH-ARM / FISHERS | P=0.419N P=0.080N P=0.613N P=0.262N |P=0.178N P=0.006N** P=0.022N* P=0.037N* | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Thyroid Gland: Follicle | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 1/50 (2%) 1/50 (2%) |1/49 (2%) 1/50 (2%) 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 1/40.89 3/39.45 1/39.45 1/42.44 |1/44.01 1/45.74 2/45.30 2/44.02 | |POLY-3 PERCENT (g) | 2.5% 7.6% 2.5% 2.4% |2.3% 2.2% 4.4% 4.5% | |TERMINAL (d) | 1/30 (3%) 3/21 (14%) 1/21 (5%) 1/30 (3%) |1/33 (3%) 1/39 (3%) 2/35 (6%) 2/34 (6%) | |FIRST INCIDENCE | 729 (T) 729 (T) 729 (T) 729 (T) |730 (T) 730 (T) 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.376N P=0.186 P=0.681 P=0.762 |P=0.366 P=0.724N P=0.521 P=0.510 | |POLY 3 | P=0.415N P=0.292 P=0.753 P=0.753N |P=0.376 P=0.752N P=0.510 P=0.500 | |POLY 1.5 | P=0.418N P=0.305 P=0.760 P=0.753N |P=0.382 P=0.754N P=0.507 P=0.503 | |POLY 6 | P=0.416N P=0.268 P=0.739 P=0.755N |P=0.369 P=0.748N P=0.515 P=0.497 | |LOGISTIC REGRESSION| P=0.376N P=0.186 P=0.681 P=0.762 |P=0.366 P=0.724N P=0.521 P=0.510 | |COCH-ARM / FISHERS | P=0.430N P=0.309 P=0.753N P=0.753N |P=0.388 P=0.747N P=0.508 P=0.508 | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 50 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Uterus | | Hydrometra | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |5/49 (10%) 3/50 (6%) 5/50 (10%) 6/50 (12%) | |POLY-3 RATE (b) | |5/44.18 3/46.05 5/45.32 6/44.29 | |POLY-3 PERCENT (g) | |11.3% 6.5% 11.0% 13.6% | |TERMINAL (d) | |4/33 (12%) 2/39 (5%) 4/35 (11%) 4/34 (12%) | |FIRST INCIDENCE | |685 646 725 674 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.280 P=0.286N P=0.596N P=0.510 | |POLY 3 | |P=0.297 P=0.334N P=0.614N P=0.502 | |POLY 1.5 | |P=0.305 P=0.340N P=0.618N P=0.506 | |POLY 6 | |P=0.285 P=0.324N P=0.608N P=0.497 | |LOGISTIC REGRESSION| |P=0.285 P=0.334N P=0.597N P=0.492 | |COCH-ARM / FISHERS | |P=0.316 P=0.346N P=0.617N P=0.514 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Uterus | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |1/49 (2%) 5/50 (10%) 4/50 (8%) 7/50 (14%) | |POLY-3 RATE (b) | |1/44.37 5/45.74 4/45.32 7/44.94 | |POLY-3 PERCENT (g) | |2.3% 10.9% 8.8% 15.6% | |TERMINAL (d) | |0/33 (0%) 5/39 (13%) 3/35 (9%) 5/34 (15%) | |FIRST INCIDENCE | |630 730 (T) 725 590 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.049 * P=0.139 P=0.199 P=0.038 * | |POLY 3 | |P=0.055 P=0.108 P=0.185 P=0.031 * | |POLY 1.5 | |P=0.057 P=0.107 P=0.184 P=0.032 * | |POLY 6 | |P=0.054 P=0.110 P=0.187 P=0.030 * | |LOGISTIC REGRESSION| |P=0.055 P=0.112 P=0.186 P=0.037 * | |COCH-ARM / FISHERS | |P=0.059 P=0.107 P=0.187 P=0.032 * | |=================================================================================================================================| Date: 01/25/01 EXPERIMENT: 05211 TEST: 05 Page 51 Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - EMODIN Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 280 830 2500 |0 280 830 2500 | | | PPM PPM PPM PPM |PPM PPM PPM PPM | |=================================================================================================================================| | | |Uterus | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |1/49 (2%) 0/50 (0%) 1/50 (2%) 2/50 (4%) | |POLY-3 RATE (b) | |1/44.37 0/45.74 1/45.30 2/44.02 | |POLY-3 PERCENT (g) | |2.3% 0.0% 2.2% 4.5% | |TERMINAL (d) | |0/33 (0%) 0/39 (0%) 1/35 (3%) 2/34 (6%) | |FIRST INCIDENCE | |630 --- 730 (T) 730 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.221 P=0.500N P=0.751N P=0.499 | |POLY 3 | |P=0.229 P=0.494N P=0.756N P=0.497 | |POLY 1.5 | |P=0.234 P=0.495N P=0.757N P=0.501 | |POLY 6 | |P=0.223 P=0.492N P=0.754N P=0.492 | |LOGISTIC REGRESSION| |P=0.235 P=0.482N P=0.754N P=0.507 | |COCH-ARM / FISHERS | |P=0.238 P=0.495N P=0.747N P=0.508 | |=================================================================================================================================| (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).